Jessica E Treisman, Ph.D.

Requirements for mediator complex subunits distinguish three classes of notch target genes at the Drosophila wing margin
Janody F; Treisman JE
2011 Sep;240(9):2051-29 L, Developmental dynamics
Spatial and temporal gene regulation relies on a combinatorial code of sequence-specific transcription factors that must be integrated by the general transcriptional machinery. A key link between the two is the mediator complex, which consists of a core complex that reversibly associates with the accessory kinase module. We show here that genes activated by Notch signaling at the dorsal-ventral boundary of the Drosophila wing disc fall into three classes that are affected differently by the loss of kinase module subunits. One class requires all four kinase module subunits for activation, while the others require only Med12 and Med13, either for activation or for repression. These distinctions do not result from different requirements for the Notch coactivator Mastermind or the corepressors Hairless and Groucho. We propose that interactions with the kinase module through distinct cofactors allow the DNA-binding protein Suppressor of Hairless to carry out both its activator and repressor functions. Developmental Dynamics, 2011. (c) 2011 Wiley-Liss, Inc
— id: 137020, year: 2011, vol: 240, page: 2051, stat: Journal Article,

Not just the messenger: RNA takes control
Richter, Joel D; Treisman, Jessica E
2011 Aug;21(4):363-365, Current opinion in genetics & development
— id: 137019, year: 2011, vol: 21, page: 363, stat: Journal Article,

Three Drosophila liprins interact to control synapse formation
Astigarraga, Sergio; Hofmeyer, Kerstin; Farajian, Reza; Treisman, Jessica E
2010 Nov 17;30(46):15358-15368, Journal of neuroscience
Liprin-alpha proteins are adaptors that interact with the receptor protein tyrosine phosphatase leukocyte common antigen-related (LAR) and other synaptic proteins to promote synaptic partner selection and active zone assembly. Liprin-beta proteins bind to and share homology with Liprin-alpha proteins, but their functions at the synapse are unknown. The Drosophila genome encodes single Liprin-alpha and Liprin-beta homologs, as well as a third related protein that we named Liprin-gamma. We show that both Liprin-beta and Liprin-gamma physically interact with Liprin-alpha and that Liprin-gamma also binds to LAR. Liprin-alpha mutations have been shown to disrupt synaptic target layer selection by R7 photoreceptors and to reduce the size of larval neuromuscular synapses. We have generated null mutations in Liprin-beta and Liprin-gamma to investigate their role in these processes. We find that, although Liprin-alpha mutant R7 axons terminate before reaching the correct target layer, Liprin-beta mutant R7 axons grow beyond their target layer. Larval neuromuscular junction size is reduced in both Liprin-alpha and Liprin-beta mutants, and further reduced in double mutants, suggesting independent functions for these Liprins. Genetic interactions demonstrate that both Liprin proteins act through the exchange factor Trio to promote stable target selection by R7 photoreceptor axons and growth of neuromuscular synapses. Photoreceptor and neuromuscular synapses develop normally in Liprin-gamma mutants; however, removing Liprin-gamma improves R7 targeting in Liprin-alpha mutants, and restores normal neuromuscular junction size to Liprin-beta mutants, suggesting that Liprin-gamma counteracts the functions of the other two Liprins. We propose that context-dependent interactions between the three Liprins modulate their functions in synapse formation
— id: 114592, year: 2010, vol: 30, page: 15358, stat: Journal Article,

Missed connections: photoreceptor axon seeks target neuron for synaptogenesis
Astigarraga, Sergio; Hofmeyer, Kerstin; Treisman, Jessica E
2010 Aug;20(4):400-407, Current opinion in genetics & development
Extending axons must choose the appropriate synaptic target cells in order to assemble functional neural circuitry. The axons of the Drosophila color-sensitive photoreceptors R7 and R8 project as a single fascicle from each ommatidium, but their terminals are segregated into distinct layers within their target region. Recent studies have begun to reveal the molecular mechanisms that establish this projection pattern. Both homophilic adhesion molecules and specific ligand-receptor interactions make important contributions to stabilizing R7 and R8 terminals in the appropriate target layers. These cell recognition molecules are regulated by the same transcription factors that control R7 and R8 cell fates. Autocrine and repulsive signaling mechanisms prevent photoreceptor terminals from encroaching on their neighbors, preserving the spatial resolution of visual information
— id: 111346, year: 2010, vol: 20, page: 400, stat: Journal Article,

Mammalian SWI/SNF-A Subunit BAF250/ARID1 Is an E3 Ubiquitin Ligase That Targets Histone H2B
Li, Xuan Shirley; Trojer, Patrick; Matsumura, Tatsushi; Treisman, Jessica E; Tanese, Naoko
2010 Apr;30(7):1673-1688, Molecular & cellular biology
The mammalian SWI/SNF chromatin-remodeling complex facilitates DNA access by transcription factors and the transcription machinery. The characteristic member of human SWI/SNF-A is BAF250/ARID1, of which there are two isoforms, BAF250a/ARID1a and BAF250b/ARID1b. Here we report that BAF250b complexes purified from mammalian cells contain elongin C (Elo C), a BC box binding component of an E3 ubiquitin ligase. BAF250b was found to have a BC box motif, associate with Elo C in a BC box-dependent manner, and, together with cullin 2 and Roc1, assemble into an E3 ubiquitin ligase. The BAF250b BC box mutant protein was unstable in vivo and was autoubiquitinated in a manner similar to that for the VHL BC box mutants. The discovery that BAF250 is part of an E3 ubiquitin ligase adds an enzymatic function to the chromatin-remodeling complex SWI/SNF-A. The immunopurified BAF250b E3 ubiquitin ligase was found to target histone H2B at lysine 120 for monoubiquitination in vitro. To date, all H2B monoubiquitination was attributed to the human homolog of yeast Bre1 (RNF20/40). Mutation of Drosophila osa, the homolog of BAF250, or depletion of BAF250 by RNA interference (RNAi) in cultured human cells resulted in global decreases in monoubiquitinated H2B, implicating BAF250 in the cross talk of histone modifications
— id: 107927, year: 2010, vol: 30, page: 1673, stat: Journal Article,

The transcriptional co-factor Chip acts with LIM-homeodomain proteins to set the boundary of the eye field in Drosophila
Roignant, Jean-Yves; Legent, Kevin; Janody, Florence; Treisman, Jessica E
2010 Jan;137(2):273-281, Development
Development involves the establishment of boundaries between fields specified to differentiate into distinct tissues. The Drosophila larval eye-antennal imaginal disc must be subdivided into regions that differentiate into the adult eye, antenna and head cuticle. We have found that the transcriptional co-factor Chip is required for cells at the ventral eye-antennal disc border to take on a head cuticle fate; clones of Chip mutant cells in this region instead form outgrowths that differentiate into ectopic eye tissue. Chip acts independently of the transcription factor Homothorax, which was previously shown to promote head cuticle development in the same region. Chip and its vertebrate CLIM homologues have been shown to form complexes with LIM-homeodomain transcription factors, and the domain of Chip that mediates these interactions is required for its ability to suppress the eye fate. We show that two LIM-homeodomain proteins, Arrowhead and Lim1, are expressed in the region of the eye-antennal disc affected in Chip mutants, and that both require Chip for their ability to suppress photoreceptor differentiation when misexpressed in the eye field. Loss-of-function studies support the model that Arrowhead and Lim1 act redundantly, using Chip as a co-factor, to prevent retinal differentiation in regions of the eye disc destined to become ventral head tissue
— id: 106099, year: 2010, vol: 137, page: 273, stat: Journal Article,

Exon junction complex subunits are required to splice Drosophila MAP kinase, a large heterochromatic gene
Roignant, Jean-Yves; Treisman, Jessica E
2010 Oct 15;143(2):238-250, Cell
The exon junction complex (EJC) is assembled on spliced mRNAs upstream of exon-exon junctions and can regulate their subsequent translation, localization, or degradation. We isolated mutations in Drosophila mago nashi (mago), which encodes a core EJC subunit, based on their unexpectedly specific effects on photoreceptor differentiation. Loss of Mago prevents epidermal growth factor receptor signaling, due to a large reduction in MAPK mRNA levels. MAPK expression also requires the EJC subunits Y14 and eIF4AIII and EJC-associated splicing factors. Mago depletion does not affect the transcription or stability of MAPK mRNA but alters its splicing pattern. MAPK expression from an exogenous promoter requires Mago only when the template includes introns. MAPK is the primary functional target of mago in eye development; in cultured cells, Mago knockdown disproportionately affects other large genes located in heterochromatin. These data support a nuclear role for EJC components in splicing a specific subset of introns
— id: 113949, year: 2010, vol: 143, page: 238, stat: Journal Article,

The receptor protein tyrosine phosphatase LAR promotes R7 photoreceptor axon targeting by a phosphatase-independent signaling mechanism
Hofmeyer, Kerstin; Treisman, Jessica E
2009 Nov 17;106(46):19399-19404, Proceedings of the National Academy of Sciences of the United States of America
Receptor protein tyrosine phosphatases (RPTPs) control many aspects of nervous system development. At the Drosophila neuromuscular junction (NMJ), regulation of synapse growth and maturation by the RPTP LAR depends on catalytic phosphatase activity and on the extracellular ligands Syndecan and Dally-like. We show here that the function of LAR in controlling R7 photoreceptor axon targeting in the visual system differs in several respects. The extracellular domain of LAR important for this process is distinct from the domains known to bind Syndecan and Dally-like, suggesting the involvement of a different ligand. R7 targeting does not require LAR phosphatase activity, but instead depends on the phosphatase activity of another RPTP, PTP69D. In addition, a mutation that prevents dimerization of the intracellular domain of LAR interferes with its ability to promote R7 targeting, although it does not disrupt phosphatase activity or neuromuscular synapse growth. We propose that LAR function in R7 is independent of its phosphatase activity, but requires structural features that allow dimerization and may promote the assembly of downstream effectors
— id: 105364, year: 2009, vol: 106, page: 19399, stat: Journal Article,

Pattern formation in the Drosophila eye disc
Roignant, Jean-Yves; Treisman, Jessica E
2009 ;53(5-6):795-804, International journal of developmental biology
Differentiation of the Drosophila compound eye from the eye imaginal disc is a progressive process: columns of cells successively differentiate in a posterior to anterior sequence, clusters of cells form at regularly spaced intervals within each column, and individual photoreceptors differentiate in a defined order within each cluster. The progression of differentiation across the eye disc is driven by a positive autoregulatory loop of expression of the secreted molecule Hedgehog, which is temporally delayed by the intercalation of a second signal, Spitz. Hedgehog refines the spatial position at which each column initiates its differentiation by inducing secondary signals that act over different ranges to control the expression of positive and negative regulators. The position of clusters within each column is controlled by secreted inhibitory signals from clusters in the preceding column, and a single founder neuron, R8, is singled out within each cluster by Notch-mediated lateral inhibition. R8 then sequentially recruits surrounding cells to differentiate by producing a short-range signal, Spitz, which induces a secondary short-range signal, Delta. Intrinsic transcription factors act in combination with these two signals to produce cell-type diversity within the ommatidium. The Hedgehog and Spitz signals are transported along the photoreceptor axons and reused within the brain as long-range and local cues to trigger the differentiation and assembly of target neurons
— id: 100617, year: 2009, vol: 53, page: 795, stat: Journal Article,

Drosophila lysophospholipid acyltransferases are specifically required for germ cell development
Steinhauer, Josefa; Gijon, Miguel A; Riekhof, Wayne R; Voelker, Dennis R; Murphy, Robert C; Treisman, Jessica E
2009 Dec;20(24):5224-5235, Molecular biology of the cell
Enzymes of the membrane-bound O-acyltransferase (MBOAT) family add fatty acyl chains to a diverse range of protein and lipid substrates. A chromosomal translocation disrupting human MBOAT1 results in a novel syndrome characterized by male sterility and brachydactyly. We have found that the Drosophila homologues of MBOAT1, Oysgedart (Oys), Nessy (Nes), and Farjavit (Frj), are lysophospholipid acyltransferases. When expressed in yeast, these MBOATs esterify specific lysophospholipids preferentially with unsaturated fatty acids. Generating null mutations for each gene allowed us to identify redundant functions for Oys and Nes in two distinct aspects of Drosophila germ cell development. Embryos lacking both oys and nes show defects in the ability of germ cells to migrate into the mesoderm, a process guided by lipid signals. In addition, oys nes double mutant adult males are sterile due to specific defects in spermatid individualization. oys nes mutant testes, as well as single, double, and triple mutant whole adult animals, show an increase in the saturated fatty acid content of several phospholipid species. Our findings suggest that lysophospholipid acyltransferase activity is essential for germline development and could provide a mechanistic explanation for the etiology of the human MBOAT1 mutation
— id: 105963, year: 2009, vol: 20, page: 5224, stat: Journal Article,

Lipid-modified morphogens: functions of fats
Steinhauer, Josefa; Treisman, Jessica E
2009 Aug;19(4):308-314, Current opinion in genetics & development
Despite their location in the aqueous extracellular environment, a number of secreted proteins carry hydrophobic lipid modifications. These modifications include glycosylphosphatidylinositol, cholesterol, and both saturated and unsaturated fatty acids, and they are attached in the secretory pathway by different classes of enzymes. Lipid attachments make crucial contributions to protein function in vivo through a diverse array of mechanisms. They can promote protein maturation and secretion, membrane tethering, targeting to specific membrane subdomains, or receptor binding and activation. Additionally, secretion of lipid-modified morphogens of the Wnt and Hh families requires dedicated accessory proteins and may involve their packaging into lipoprotein particles for long-range transport
— id: 101885, year: 2009, vol: 19, page: 308, stat: Journal Article,

Pygopus activates Wingless target gene transcription through the mediator complex subunits Med12 and Med13
Carrera, Ines; Janody, Florence; Leeds, Nina; Duveau, Fabien; Treisman, Jessica E
2008 May 6;105(18):6644-6649, Proceedings of the National Academy of Sciences of the United States of America
Wnt target gene transcription is mediated by nuclear translocation of stabilized beta-catenin, which binds to TCF and recruits Pygopus, a cofactor with an unknown mechanism of action. The mediator complex is essential for the transcription of RNA polymerase II-dependent genes; it associates with an accessory subcomplex consisting of the Med12, Med13, Cdk8, and Cyclin C subunits. We show here that the Med12 and Med13 subunits of the Drosophila mediator complex, encoded by kohtalo and skuld, are essential for the transcription of Wingless target genes. kohtalo and skuld act downstream of beta-catenin stabilization both in vivo and in cell culture. They are required for transcriptional activation by the N-terminal domain of Pygopus, and their physical interaction with Pygopus depends on this domain. We propose that Pygopus promotes Wnt target gene transcription by recruiting the mediator complex through interactions with Med12 and Med13
— id: 79160, year: 2008, vol: 105, page: 6644, stat: Journal Article,

Message in a nucleus: signaling to the transcriptional machinery
Carrera, Ines; Treisman, Jessica E
2008 Oct;18(5):397-403, Current opinion in genetics & development
Tissue differentiation and signal transduction involve dramatic changes in gene expression. These changes can be brought about by the expression or activation of sequence-specific transcription factors. In order to regulate their target genes, such factors must navigate the intricate chromatin environment and engage the complex basal transcriptional machinery. We discuss three mechanisms through which signaling pathways can interact with complexes that alter chromatin structure or recruit RNA polymerase II. Signals that promote differentiation may alter the properties of such transcriptional regulatory complexes by incorporating tissue-specific subunits. Alternatively, adaptor subunits specialized to interact with specific transcription factors may allow a single complex to respond to multiple signals. Finally, individual regulatory proteins may integrate a variety of signals, allowing crosstalk between pathways
— id: 93215, year: 2008, vol: 18, page: 397, stat: Journal Article,

Two subunits specific to the PBAP chromatin remodeling complex have distinct and redundant functions during drosophila development
Carrera, Ines; Zavadil, Jiri; Treisman, Jessica E
2008 Sep;28(17):5238-5250, Molecular & cellular biology
Chromatin remodeling complexes control the availability of DNA binding sites to transcriptional regulators. Two distinct conserved forms of the SWI/SNF class of complexes are characterized by the presence of specific accessory subunits. In Drosophila, the core Brahma complex associates either with Osa to form the BAP complex or with Bap170 and Bap180 to form the PBAP complex. osa mutations reproduce only a subset of the developmental phenotypes caused by mutations in subunits of the core complex. To test whether the PBAP complex performs the remaining functions, we generated mutations in bap170 and bap180. Surprisingly, we found that Bap180 is not essential for viability, although it is required in ovarian follicle cells for normal eggshell development. Bap170 is necessary to stabilize the Bap180 protein, but a mutant form that retains this function is sufficient for both survival and fertility. The two subunits act redundantly to allow metamorphosis; using gene expression profiling of bap170 bap180 double mutants, we found that the PBAP complex regulates genes involved in tissue remodeling and immune system function. Finally, we generated mutants lacking Bap170, Bap180, and Osa in the germ line to demonstrate that the core Brahma complex can function in oogenesis without any of these accessory subunits
— id: 82624, year: 2008, vol: 28, page: 5238, stat: Journal Article,

Sensory systems: seeing the world in a new light
Hofmeyer, Kerstin; Treisman, Jessica E
2008 Oct 14;18(19):R919-R921, Current biology. CB
Most terminally differentiated sensory neurons express a single sensory receptor molecule. A Drosophila photoreceptor organ breaks this rule by switching to expressing a different type of Rhodopsin as it metamorphoses from larva to adult
— id: 91452, year: 2008, vol: 18, page: R919, stat: Journal Article,

Wingless signaling in Drosophila eye development
Legent, Kevin; Treisman, Jessica E
2008 ;469:141-161, Methods in molecular biology
The secreted morphogen Wingless (Wg) has a variety of functions throughout Drosophila eye development, controlling tissue specification, growth, and patterning. Wg plays a critical role in subdividing the eye imaginal disc into separate primordia that will give rise to the adult retina and the surrounding head capsule. During larval development, wg is expressed in the anterior lateral margins of the eye disc, regions that will give rise to head cuticle; Wg signaling promotes the head fate and prevents these marginal regions from initiating ectopic photoreceptor differentiation. Expression of wg at the dorsal margin is earlier and stronger than at the ventral margin, allowing Wg to contribute to specifying the dorsal domain of the eye disc. Finally, during the pupal stages, wg expression surrounds the entire eye and a concentric gradient of Wg establishes several distinct peripheral retinal cell fates. This chapter reviews these aspects of Wg function and describes how to generate clones of cells mutant for genes encoding components of the Wg signaling pathway in the eye disc and examine their effects on photoreceptor differentiation by immunohistochemistry
— id: 92185, year: 2008, vol: 469, page: 141, stat: Journal Article,

Myopic acts in the endocytic pathway to enhance signaling by the Drosophila EGF receptor
Miura, Grant I; Roignant, Jean-Yves; Wassef, Michel; Treisman, Jessica E
2008 Jun;135(11):1913-1922, Development
Endocytosis of activated receptors can control signaling levels by exposing the receptors to novel downstream molecules or by instigating their degradation. Epidermal growth factor receptor (EGFR) signaling has crucial roles in development and is misregulated in many cancers. We report here that Myopic, the Drosophila homolog of the Bro1-domain tyrosine phosphatase HD-PTP, promotes EGFR signaling in vivo and in cultured cells. myopic is not required in the presence of activated Ras or in the absence of the ubiquitin ligase Cbl, indicating that it acts on internalized EGFR, and its overexpression enhances the activity of an activated form of EGFR. Myopic is localized to intracellular vesicles adjacent to Rab5-containing early endosomes, and its absence results in the enlargement of endosomal compartments. Loss of Myopic prevents cleavage of the EGFR cytoplasmic domain, a process controlled by the endocytic regulators Cbl and Sprouty. We suggest that Myopic promotes EGFR signaling by mediating its progression through the endocytic pathway
— id: 78373, year: 2008, vol: 135, page: 1913, stat: Journal Article,

The conserved microRNA miR-8 tunes atrophin levels to prevent neurodegeneration in Drosophila
Karres, Janina S; Hilgers, Valerie; Carrera, Ines; Treisman, Jessica; Cohen, Stephen M
2007 Oct 5;131(1):136-145, Cell
microRNAs (miRNAs) bind to specific messenger RNA targets to posttranscriptionally modulate their expression. Understanding the regulatory relationships between miRNAs and targets remains a major challenge. Many miRNAs reduce expression of their targets to inconsequential levels. It has also been proposed that miRNAs might adjust target expression to an optimal level. Here we analyze the consequences of mutating the conserved miRNA miR-8 in Drosophila. We identify atrophin as a direct target of miR-8. miR-8 mutant phenotypes are attributable to elevated atrophin activity, resulting in elevated apoptosis in the brain and in behavioral defects. Reduction of atrophin levels in miR-8-expressing cells to below the level generated by miR-8 regulation is detrimental, providing evidence for a 'tuning target' relationship between them. Drosophila atrophin is related to the atrophin family of mammalian transcriptional regulators, implicated in the neurodegenerative disorder DRPLA. The regulatory relationship between miR-8 and atrophin orthologs is conserved in mammals
— id: 137021, year: 2007, vol: 131, page: 136, stat: Journal Article,

Liprin-alpha has LAR-independent functions in R7 photoreceptor axon targeting
Hofmeyer, Kerstin; Maurel-Zaffran, Corinne; Sink, Helen; Treisman, Jessica E
2006 Aug 1;103(31):11595-11600, Proceedings of the National Academy of Sciences of the United States of America
In the Drosophila visual system, the color-sensing photoreceptors R7 and R8 project their axons to two distinct layers in the medulla. Loss of the receptor tyrosine phosphatase LAR from R7 photoreceptors causes their axons to terminate prematurely in the R8 layer. Here we identify a null mutation in the Liprin-alpha gene based on a similar R7 projection defect. Liprin-alpha physically interacts with the inactive D2 phosphatase domain of LAR, and this domain is also essential for R7 targeting. However, another LAR-dependent function, egg elongation, requires neither Liprin-alpha nor the LAR D2 domain. Although human and Caenorhabditis elegans Liprin-alpha proteins have been reported to control the localization of LAR, we find that LAR localizes to focal adhesions in Drosophila S2R+ cells and to photoreceptor growth cones in vivo independently of Liprin-alpha. In addition, Liprin-alpha overexpression or loss of function can affect R7 targeting in the complete absence of LAR. We conclude that Liprin-alpha does not simply act by regulating LAR localization but also has LAR-independent functions
— id: 68984, year: 2006, vol: 103, page: 11595, stat: Journal Article,

Actin capping protein alpha maintains vestigial-expressing cells within the Drosophila wing disc epithelium
Janody, Florence; Treisman, Jessica E
2006 Sep;133(17):3349-3357, Development
Tissue patterning must be translated into morphogenesis through cell shape changes mediated by remodeling of the actin cytoskeleton. We have found that Capping protein alpha (Cpa) and Capping protein beta (Cpb), which prevent extension of the barbed ends of actin filaments, are specifically required in the wing blade primordium of the Drosophila wing disc. cpa or cpb mutant cells in this region, but not in the remainder of the wing disc, are extruded from the epithelium and undergo apoptosis. Excessive actin filament polymerization is not sufficient to explain this phenotype, as loss of Cofilin or Cyclase-associated protein does not cause cell extrusion or death. Misexpression of Vestigial, the transcription factor that specifies the wing blade, both increases cpa transcription and makes cells dependent on cpa for their maintenance in the epithelium. Our results suggest that Vestigial specifies the cytoskeletal changes that lead to morphogenesis of the adult wing
— id: 95043, year: 2006, vol: 133, page: 3349, stat: Journal Article,

Palmitoylation of the EGFR ligand Spitz by Rasp increases Spitz activity by restricting its diffusion
Miura, Grant I; Buglino, John; Alvarado, Diego; Lemmon, Mark A; Resh, Marilyn D; Treisman, Jessica E
2006 Feb;10(2):167-176, Developmental cell
Lipid modifications such as palmitoylation or myristoylation target intracellular proteins to cell membranes. Secreted ligands of the Hedgehog and Wnt families are also palmitoylated; this modification, which requires the related transmembrane acyltransferases Rasp and Porcupine, can enhance their secretion, transport, or activity. We show here that rasp is also essential for the developmental functions of Spitz, a ligand for the Drosophila epidermal growth factor receptor (EGFR). In cultured cells, Rasp promotes palmitate addition to the N-terminal cysteine residue of Spitz, and this cysteine is required for Spitz activity in vivo. Palmitoylation reduces Spitz secretion and enhances its plasma membrane association, but does not alter its ability to activate the EGFR in vitro. In vivo, overexpressed unpalmitoylated Spitz has an increased range of action but reduced activity. These data suggest a role for palmitoylation in restricting Spitz diffusion, allowing its local concentration to reach the threshold required for biological function
— id: 63073, year: 2006, vol: 10, page: 167, stat: Journal Article,

Lipid modification of secreted signaling proteins
Miura, Grant I; Treisman, Jessica E
2006 Jun;5(11):1184-1188, Cell cycle
Proteins of the Hedgehog, Wnt and Epidermal Growth Factor Receptor (EGFR) ligand families are secreted signals that induce concentration-dependent responses in surrounding cells. Although these proteins must diffuse through the aqueous extracellular environment, recent work has shown that hydrophobic lipid modifications are essential for their functions. All three classes of ligands are palmitoylated in the secretory pathway by related enzymes, and Hedgehog also carries a C-terminal cholesterol modification as a result of its autocatalytic cleavage. Palmitoylation is required for Wingless secretion and contributes to the signaling activity of Hedgehog and Wnt3a, but is not required for secretion or receptor activation by the EGFR ligand Spitz. While lipid modifications enhance the long-range activity of Sonic hedgehog, they restrict the range and increase the local concentration of Spitz. We discuss the diverse functions and the possible extent of palmitoylation of secreted ligands
— id: 67531, year: 2006, vol: 5, page: 1184, stat: Journal Article,

The novel SAM domain protein Aveugle is required for Raf activation in the Drosophila EGF receptor signaling pathway
Roignant, Jean-Yves; Hamel, Sophie; Janody, Florence; Treisman, Jessica E
2006 Apr 1;20(7):795-806, Genes & development
Activation of the Raf kinase by GTP-bound Ras is a poorly understood step in receptor tyrosine kinase signaling pathways. One such pathway, the epidermal growth factor receptor (EGFR) pathway, is critical for cell differentiation, survival, and cell cycle regulation in many systems, including the Drosophila eye. We have identified a mutation in a novel gene, aveugle, based on its requirement for normal photoreceptor differentiation. The phenotypes of aveugle mutant cells in the eye and wing imaginal discs resemble those caused by reduction of EGFR pathway function. We show that aveugle is required between ras and raf for EGFR signaling in the eye and for mitogen-activated protein kinase phosphorylation in cell culture. aveugle encodes a small protein with a sterile alpha motif (SAM) domain that can physically interact with the scaffold protein connector enhancer of Ksr (Cnk). We propose that Aveugle acts together with Cnk to promote Raf activation, perhaps by recruiting an activating kinase
— id: 64141, year: 2006, vol: 20, page: 795, stat: Journal Article,

A mosaic genetic screen reveals distinct roles for trithorax and polycomb group genes in Drosophila eye development
Janody, Florence; Lee, Jeffrey D; Jahren, Neal; Hazelett, Dennis J; Benlali, Aude; Miura, Grant I; Draskovic, Irena; Treisman, Jessica E
2004 Jan;166(1):187-200, Genetics
The wave of differentiation that traverses the Drosophila eye disc requires rapid transitions in gene expression that are controlled by a number of signaling molecules also required in other developmental processes. We have used a mosaic genetic screen to systematically identify autosomal genes required for the normal pattern of photoreceptor differentiation, independent of their requirements for viability. In addition to genes known to be important for eye development and to known and novel components of the Hedgehog, Decapentaplegic, Wingless, Epidermal growth factor receptor, and Notch signaling pathways, we identified several members of the Polycomb and trithorax classes of genes encoding general transcriptional regulators. Mutations in these genes disrupt the transitions between zones along the anterior-posterior axis of the eye disc that express different combinations of transcription factors. Different trithorax group genes have very different mutant phenotypes, indicating that target genes differ in their requirements for chromatin remodeling, histone modification, and coactivation factors
— id: 43224, year: 2004, vol: 166, page: 187, stat: Journal Article,

Excessive Myosin activity in mbs mutants causes photoreceptor movement out of the Drosophila eye disc epithelium
Lee, Arnold; Treisman, Jessica E
2004 Jul;15(7):3285-3295, Molecular biology of the cell
Neuronal cells must extend a motile growth cone while maintaining the cell body in its original position. In migrating cells, myosin contraction provides the driving force that pulls the rear of the cell toward the leading edge. We have characterized the function of myosin light chain phosphatase, which down-regulates myosin activity, in Drosophila photoreceptor neurons. Mutations in the gene encoding the myosin binding subunit of this enzyme cause photoreceptors to drop out of the eye disc epithelium and move toward and through the optic stalk. We show that this phenotype is due to excessive phosphorylation of the myosin regulatory light chain Spaghetti squash rather than another potential substrate, Moesin, and that it requires the nonmuscle myosin II heavy chain Zipper. Myosin binding subunit mutant cells continue to express apical epithelial markers and do not undergo ectopic apical constriction. In addition, mutant cells in the wing disc remain within the epithelium and differentiate abnormal wing hairs. We suggest that excessive myosin activity in photoreceptor neurons may pull the cell bodies toward the growth cones in a process resembling normal cell migration
— id: 43225, year: 2004, vol: 15, page: 3285, stat: Journal Article,

Lightoid and Claret: a rab GTPase and its putative guanine nucleotide exchange factor in biogenesis of Drosophila eye pigment granules
Ma, Jinping; Plesken, Heide; Treisman, Jessica E; Edelman-Novemsky, Irit; Ren, Mindong
2004 Aug 10;101(32):11652-11657, Proceedings of the National Academy of Sciences of the United States of America
To elucidate the biogenetic pathways for the generation of lysosome-related organelles, we have chosen to study the Drosophila eye pigment granules because they are lysosome-related and the fruit fly provides the advantages of a genetic system in which many mutations affect eye color. Here, we report the molecular identification of two classic Drosophila eye-color genes required for pigment granule biogenesis, claret and lightoid; the former encodes a protein containing seven repeats with sequence similarity to those that characterize regulator of chromosome condensation 1 (RCC1, a guanine nucleotide exchange factor for the small GTPase, Ran), and the latter encodes a rab GTPase, Rab-RP1. We demonstrate in transfected cells that Claret, through its RCC1-like domain, interacts preferentially with the nucleotide-free form of Rab-RP1, and this interaction involves Claret's first three RCC1-like repeats that are also critical for Claret's function in pigment granule biogenesis in transgenic rescue experiments. In addition, double-mutant analyses suggest that the gene products of claret and lightoid function in the same pathway, which is different from that of garnet and ruby (which encode the delta- and beta-subunit of the tetrameric adaptor protein 3 complex, respectively). Taken together, our results suggest that Claret functions as a guanine nucleotide exchange factor for Lightoid/Rab-RP1 in an adaptor protein 3-independent vesicular trafficking pathway of pigment granule biogenesis
— id: 45311, year: 2004, vol: 101, page: 11652, stat: Journal Article,

Coming to our senses
Treisman, Jessica E
2004 Aug;26(8):825-828, Bioessays
Sensory organs are specialized to receive different kinds of input from the outside world. However, common features of their development suggest that they could have a shared evolutionary origin. In a recent paper, Niwa et al. show that three Drosophila adult sensory organs all rely on the spatial signals Decapentaplegic and Wingless to specify their position, and the temporal signal ecdysone to initiate their development. The proneural gene atonal is an important site for integration of these regulatory inputs. These results suggest the existence of a primitive sensory organ precursor, which would differentiate according to the identity of its segment of origin. The authors argue that the eyeless gene controls eye disc identity, indirectly producing an eye from the sensory organ precursor within this disc
— id: 45313, year: 2004, vol: 26, page: 825, stat: Journal Article,

How to make an eye
Treisman, Jessica E
2004 Aug;131(16):3823-3827, Development
The eye is an organ of such remarkable complexity and apparently flawless design that it presents a challenge to both evolutionary biologists trying to explain its phylogenetic origins, and developmental biologists hoping to understand its formation during ontogeny. Since the discovery that the transcription factor Pax6 plays a crucial role in specifying the eye throughout the animal kingdom, both groups of biologists have been converging on the conserved mechanisms behind eye formation. Their latest meeting was at the Instituto Juan March in Madrid, at a workshop organized by Walter Gehring (Biozentrum, Basel, Switzerland) and Emili Salo (Universitat de Barcelona, Spain), entitled 'The genetic control of eye development and its evolutionary implications'. The exchange of ideas provided some new insights into the construction and history of the eye
— id: 45312, year: 2004, vol: 131, page: 3823, stat: Journal Article,

Two subunits of the Drosophila mediator complex act together to control cell affinity
Janody, Florence; Martirosyan, Zara; Benlali, Aude; Treisman, Jessica E
2003 Aug;130(16):3691-3701, Development
The organizing centers for Drosophila imaginal disc development are created at straight boundaries between compartments; these are maintained by differences in cell affinity controlled by selector genes and intercellular signals. skuld and kohtalo encode homologs of TRAP240 and TRAP230, the two largest subunits of the Drosophila mediator complex; mutations in either gene cause identical phenotypes. We show here that both genes are required to establish normal cell affinity differences at the anterior-posterior and dorsal-ventral compartment boundaries of the wing disc. Mutant cells cross from the anterior to the posterior compartment, and can distort the dorsal-ventral boundary in either the dorsal or ventral direction. The Skuld and Kohtalo proteins physically interact in vivo and have synergistic effects when overexpressed, consistent with a skuld kohtalo double-mutant phenotype that is indistinguishable from either single mutant. We suggest that these two subunits do not participate in all of the activities of the mediator complex, but form a submodule that is required to regulate specific target genes, including those that control cell affinity
— id: 38097, year: 2003, vol: 130, page: 3691, stat: Journal Article,

The ubiquitin ligase Hyperplastic discs negatively regulates hedgehog and decapentaplegic expression by independent mechanisms
Lee, Jeffrey D; Amanai, Kazuhito; Shearn, Allen; Treisman, Jessica E
2002 Dec 15;129(24):5697-5706, Development
Photoreceptor differentiation in the Drosophila eye disc progresses from posterior to anterior in a wave driven by the Hedgehog and Decapentaplegic signals. Cells mutant for the hyperplastic discs gene misexpress both of these signaling molecules in anterior regions of the disc, leading to premature photoreceptor differentiation and overgrowth of surrounding tissue. The two genes are independently regulated by hyperplastic discs; decapentaplegic can still be misexpressed in cells mutant for both hyperplastic discs and hedgehog, and a repressor form of the transcription factor Cubitus interruptus can block decapentaplegic misexpression but not hedgehog misexpression. Loss of hyperplastic discs causes the accumulation of full-length Cubitus interruptus protein, but not of Smoothened, in both the eye and wing discs. hyperplastic discs encodes a HECT domain E3 ubiquitin ligase that is likely to act by targeting Cubitus interruptus and an unknown activator of hedgehog expression for proteolysis
— id: 33061, year: 2002, vol: 129, page: 5697, stat: Journal Article,

Development and evolution of the eye: Fondation des Treilles, September, 2001
Treisman, Jessica; Lang, Richard
2002 Mar;112(1-2):3-8, Mechanisms of development
— id: 32484, year: 2002, vol: 112, page: 3, stat: Journal Article,

An acylatable residue of Hedgehog is differentially required in Drosophila and mouse limb development
Lee JD; Kraus P; Gaiano N; Nery S; Kohtz J; Fishell G; Loomis CA; Treisman JE
2001 May 1;233(1):122-136, Developmental biology (Orlando)
The Drosophila Hedgehog protein and its vertebrate counterpart Sonic hedgehog are required for a wide variety of patterning events throughout development. Hedgehog proteins are secreted from cells and undergo autocatalytic cleavage and cholesterol modification to produce a mature signaling domain. This domain of Sonic hedgehog has recently been shown to acquire an N-terminal acyl group in cell culture. We have investigated the in vivo role that such acylation might play in appendage patterning in mouse and Drosophila; in both species Hedgehog proteins define a posterior domain of the limb or wing. A mutant form of Sonic hedgehog that cannot undergo acylation retains significant ability to repattern the mouse limb. However, the corresponding mutation in Drosophila Hedgehog renders it inactive in vivo, although it is normally processed. Furthermore, overexpression of the mutant form has dominant negative effects on Hedgehog signaling. These data suggest that the importance of the N-terminal cysteine of mature Hedgehog in patterning appendages differs between species.
— id: 20707, year: 2001, vol: 233, page: 122, stat: Journal Article,

Sightless has homology to transmembrane acyltransferases and is required to generate active Hedgehog protein
Lee JD; Treisman JE
2001 Jul 24;11(14):1147-1152, Current biology. CB
Proteins of the Hedgehog (Hh) family act as important developmental signals in a variety of species [1]. Hh proteins are synthesized as full-length precursors that are autocatalytically cleaved by their C-terminal domains to release the signaling N-terminal domains [2]. The addition of a cholesterol molecule to the C terminus of the signaling domain is concomitant with cleavage [3]. Vertebrate Sonic hedgehog (Shh) proteins have also been shown to acquire a fatty acid chain on the N-terminal cysteine of this domain [4], which is required for a subset of their in vivo functions [5, 6]. A mutation of the corresponding cysteine in Drosophila Hh transforms it into a dominant-negative protein [6]. We have identified a novel gene, sightless (sit), which is required for the activity of Drosophila Hh in the eye and wing imaginal discs and in embryonic segmentation. sit acts in the cells that produce Hh, but does not affect hh transcription, Hh cleavage, or the accumulation of Hh protein. sit encodes a conserved transmembrane protein with homology to a family of membrane-bound acyltransferases. The Sit protein could act by acylating Hh or by promoting other modifications or trafficking events necessary for its function
— id: 26628, year: 2001, vol: 11, page: 1147, stat: Journal Article,

The role of Wingless signaling in establishing the anteroposterior and dorsoventral axes of the eye disc
Lee JD; Treisman JE
2001 May;128(9):1519-1529, Development
The posteriorly expressed signaling molecules Hedgehog and Decapentaplegic drive photoreceptor differentiation in the Drosophila eye disc, while at the anterior lateral margins Wingless expression blocks ectopic differentiation. We show here that mutations in axin prevent photoreceptor differentiation and lead to tissue overgrowth and that both these effects are due to ectopic activation of the Wingless pathway. In addition, ectopic Wingless signaling causes posterior cells to take on an anterior identity, reorienting the direction of morphogenetic furrow progression in neighboring wild-type cells. We also show that signaling by Decapentaplegic and Hedgehog normally blocks the posterior expression of anterior markers such as Eyeless. Wingless signaling is not required to maintain anterior Eyeless expression and in combination with Decapentaplegic signaling can promote its downregulation, suggesting that additional molecules contribute to anterior identity. Along the dorsoventral axis of the eye disc, Wingless signaling is sufficient to promote dorsal expression of the Iroquois gene mirror, even in the absence of the upstream factor pannier. However, Wingless signaling does not lead to ventral mirror expression, implying the existence of ventral repressors
— id: 20789, year: 2001, vol: 128, page: 1519, stat: Journal Article,

Cell-autonomous and -nonautonomous functions of LAR in R7 photoreceptor axon targeting
Maurel-Zaffran C; Suzuki T; Gahmon G; Treisman JE; Dickson BJ
2001 Oct 25;32(2):225-235, Neuron
During Drosophila visual system development, photoreceptors R7 and R8 project axons to targets in distinct layers of the optic lobe. We show here that the LAR receptor tyrosine phosphatase is required in the eye for correct targeting of R7 axons. In LAR mutants, R7 axons initially project to their correct target layer, but then retract to the R8 target layer. This targeting defect can be fully rescued by transgenic expression of LAR in R7, and partially rescued by expression of LAR in R8. The phosphatase domains of LAR are required for its activity in R7, but not in R8. These data suggest that LAR can act both as a receptor in R7, and as a ligand provided by R8. Genetic interactions implicate both Enabled and Trio in LAR signal transduction
— id: 26591, year: 2001, vol: 32, page: 225, stat: Journal Article,

Reinventing a common strategy for patterning the eye
Pichaud F; Treisman J; Desplan C
2001 Apr 6;105(1):9-12, Cell
— id: 20792, year: 2001, vol: 105, page: 9, stat: Journal Article,

The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation
Tapon N; Ito N; Dickson BJ; Treisman JE; Hariharan IK
2001 May 4;105(3):345-355, Cell
The inherited human disease tuberous sclerosis, characterized by hamartomatous tumors, results from mutations in either TSC1 or TSC2. We have characterized mutations in the Drosophila Tsc1 and Tsc2/gigas genes. Inactivating mutations in either gene cause an identical phenotype characterized by enhanced growth and increased cell size with no change in ploidy. Overall, mutant cells spend less time in G1. Coexpression of both Tsc1 and Tsc2 restricts tissue growth and reduces cell size and cell proliferation. This phenotype is modulated by manipulations in cyclin levels. In postmitotic mutant cells, levels of Cyclin E and Cyclin A are elevated. This correlates with a tendency for these cells to reenter the cell cycle inappropriately as is observed in the human lesions
— id: 20790, year: 2001, vol: 105, page: 345, stat: Journal Article,

Drosophila homologues of the transcriptional coactivation complex subunits TRAP240 and TRAP230 are required for identical processes in eye-antennal disc development
Treisman J
2001 Feb;128(4):603-615, Development
We have identified mutations in two genes, blind spot and kohtalo, that encode Drosophila homologues of human TRAP240 and TRAP230, components of a large transcriptional coactivation complex homologous to the yeast Mediator complex. Loss of either blind spot or kohtalo has identical effects on the development of the eye-antennal disc. Eye disc cells mutant for either gene can express decapentaplegic and atonal in response to Hedgehog signaling, but they maintain inappropriate expression of these genes and fail to differentiate further. Mutant cells in the antennal disc lose expression of Distal-less and misexpress eyeless, suggesting a partial transformation towards the eye fate. blind spot and kohtalo are not required for cell proliferation or survival, and their absence cannot be rescued by activation of the Hedgehog or Notch signaling pathways. These novel and specific phenotypes suggest that TRAP240 and TRAP230 act in concert to mediate an unknown developmental signal or a combination of signals
— id: 20791, year: 2001, vol: 128, page: 603, stat: Journal Article,

act up controls actin polymerization to alter cell shape and restrict Hedgehog signaling in the Drosophila eye disc
Benlali A; Draskovic I; Hazelett DJ; Treisman JE
2000 Apr 28;101(3):271-281, Cell
Cells in the morphogenetic furrow of the Drosophila eye disc undergo a striking shape change immediately prior to their neuronal differentiation. We have isolated mutations in a novel gene, act up (acu), that is required for this shape change. acu encodes a homolog of yeast cyclase-associated protein, which sequesters monomeric actin; we show that acu is required to prevent actin filament polymerization in the eye disc. In contrast, profilin promotes actin filament polymerization, acting epistatically to acu. However, both acu and profilin are required to prevent premature Hedgehog-induced photoreceptor differentiation ahead of the morphogenetic furrow. These findings suggest that dynamic changes in actin filaments alter cell shape to control the movement of signals that coordinate a wave of differentiation
— id: 11664, year: 2000, vol: 101, page: 271, stat: Journal Article,

Osa-containing Brahma chromatin remodeling complexes are required for the repression of wingless target genes
Collins RT; Treisman JE
2000 Dec 15;14(24):3140-3152, Genes & development
The Wingless signaling pathway directs many developmental processes in Drosophila by regulating the expression of specific downstream target genes. We report here that the product of the trithorax group gene osa is required to repress such genes in the absence of the Wingless signal. The Wingless-regulated genes nubbin, Distal-less, and decapentaplegic and a minimal enhancer from the Ultrabithorax gene are misexpressed in osa mutants and repressed by ectopic Osa. Osa-mediated repression occurs downstream of the up-regulation of Armadillo but is sensitive both to the relative levels of activating Armadillo/Pangolin and repressing Groucho/Pangolin complexes present and to the responsiveness of the promoter to Wingless. Osa functions as a component of the Brahma chromatin-remodeling complex; other components of this complex are likewise required to repress Wingless target genes. These results suggest that altering the conformation of chromatin is an important mechanism by which Wingless signaling activates gene expression
— id: 39496, year: 2000, vol: 14, page: 3140, stat: Journal Article,

Drosophila bunched integrates opposing DPP and EGF signals to set the operculum boundary
Dobens LL; Peterson JS; Treisman J; Raftery LA
2000 Feb;127(4):745-754, Development
The Drosophila BMP homolog DPP can function as a morphogen, inducing multiple cell fates across a developmental field. However, it is unknown how graded levels of extracellular DPP are interpreted to organize a sharp boundary between different fates. Here we show that opposing DPP and EGF signals set the boundary for an ovarian follicle cell fate. First, DPP regulates gene expression in the follicle cells that will create the operculum of the eggshell. DPP induces expression of the enhancer trap reporter A359 and represses expression of bunched, which encodes a protein similar to the mammalian transcription factor TSC-22. Second, DPP signaling indirectly regulates A359 expression in these cells by downregulating expression of bunched. Reduced bunched function restores A359 expression in cells that lack the Smad protein MAD; ectopic expression of BUNCHED suppresses A359 expression in this region. Importantly, reduction of bunched function leads to an expansion of the operculum and loss of the collar at its boundary. Third, EGF signaling upregulates expression of bunched. We previously demonstrated that the bunched expression pattern requires the EGF receptor ligand GURKEN. Here we show that activated EGF receptor is sufficient to induce ectopic bunched expression. Thus, the balance of DPP and EGF signals sets the boundary of bunched expression. We propose that the juxtaposition of cells with high and low BUNCHED activity organizes a sharp boundary for the operculum fate
— id: 27857, year: 2000, vol: 127, page: 745, stat: Journal Article,

Early retinal development in Drosophila
Heberlein U; Treisman JE
2000 ;31:37-50, Results & problems in cell differentation
— id: 49325, year: 2000, vol: 31, page: 37, stat: Journal Article,

pannier acts upstream of wingless to direct dorsal eye disc development in Drosophila
Maurel-Zaffran C; Treisman JE
2000 Mar;127(5):1007-1016, Development
The dorsoventral midline of the Drosophila eye disc is a source of signals that stimulate growth of the eye disc, define the point at which differentiation initiates, and direct ommatidial rotation in opposite directions in the two halves of the eye disc. This boundary region seems to be established by the genes of the iroquois complex, which are expressed in the dorsal half of the disc and inhibit fringe expression there. Fringe controls the activation of Notch and the expression of its ligands, with the result that Notch is activated only at the fringe expression boundary at the midline. The secreted protein Wingless activates the dorsal expression of the iroquois genes. We show here that pannier, which encodes a GATA family transcription factor expressed at the dorsal margin of the eye disc from embryonic stages on, acts upstream of wingless to control mirror and fringe expression and establish the dorsoventral boundary. Loss of pannier function leads to the formation of an ectopic eye field and the reorganization of ommatidial polarity, and ubiquitous pannier expression can abolish the eye field. Pannier is thus the most upstream element yet described in dorsoventral patterning of the eye disc
— id: 11846, year: 2000, vol: 127, page: 1007, stat: Journal Article,

The Ste20 kinase misshapen regulates both photoreceptor axon targeting and dorsal closure, acting downstream of distinct signals
Su YC; Maurel-Zaffran C; Treisman JE; Skolnik EY
2000 Jul;20(13):4736-4744, Molecular & cellular biology
We have previously shown that the Ste20 kinase encoded by misshapen (msn) functions upstream of the c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase module in Drosophila. msn is required to activate the Drosophila JNK, Basket (Bsk), to promote dorsal closure of the embryo. A mammalian homolog of Msn, Nck interacting kinase, interacts with the SH3 domains of the SH2-SH3 adapter protein Nck. We now show that Msn likewise interacts with Dreadlocks (Dock), the Drosophila homolog of Nck. dock is required for the correct targeting of photoreceptor axons. We have performed a structure-function analysis of Msn in vivo in Drosophila in order to elucidate the mechanism whereby Msn regulates JNK and to determine whether msn, like dock, is required for the correct targeting of photoreceptor axons. We show that Msn requires both a functional kinase and a C-terminal regulatory domain to activate JNK in vivo in Drosophila. A mutation in a PXXP motif on Msn that prevents it from binding to the SH3 domains of Dock does not affect its ability to rescue the dorsal closure defect in msn embryos, suggesting that Dock is not an upstream regulator of msn in dorsal closure. Larvae with only this mutated form of Msn show a marked disruption in photoreceptor axon targeting, implicating an SH3 domain protein in this process; however, an activated form of Msn is not sufficient to rescue the dock mutant phenotype. Mosaic analysis reveals that msn expression is required in photoreceptors in order for their axons to project correctly. The data presented here genetically link msn to two distinct biological events, dorsal closure and photoreceptor axon pathfinding, and thus provide the first evidence that Ste20 kinases of the germinal center kinase family play a role in axonal pathfinding. The ability of Msn to interact with distinct classes of adapter molecules in dorsal closure and photoreceptor axon pathfinding may provide the flexibility that allows it to link to distinct upstream signaling systems
— id: 11663, year: 2000, vol: 20, page: 4736, stat: Journal Article,

Osa associates with the Brahma chromatin remodeling complex and promotes the activation of some target genes
Collins RT; Furukawa T; Tanese N; Treisman JE
1999 Dec 15;18(24):7029-7040, EMBO journal
The yeast SWI/SNF complex and its Drosophila and mammalian homologs are thought to control gene expression by altering chromatin structure, but the mechanism and specificity of this process are not fully understood. The Drosophila osa gene, like yeast SWI1, encodes an AT-rich interaction (ARID) domain protein. We present genetic and biochemical evidence that Osa is a component of the Brahma complex, the Drosophila homolog of SWI/SNF. The ARID domain of Osa binds DNA without sequence specificity in vitro, but it is sufficient to direct transcriptional regulatory domains to specific target genes in vivo. Endogenous Osa appears to promote the activation of some of these genes. We show evidence that some Brahma-containing complexes do not contain Osa and that Osa is not required to localize Brahma to chromatin. These data suggest that Osa modulates the function of the Brahma complex
— id: 8588, year: 1999, vol: 18, page: 7029, stat: Journal Article,

A Drosophila TNF-receptor-associated factor (TRAF) binds the ste20 kinase Misshapen and activates Jun kinase
Liu H; Su YC; Becker E; Treisman J; Skolnik EY
1999 Jan 28;9(2):101-104, Current biology. CB
Two families of protein kinases that are closely related to Ste20 in their kinase domain have been identified - the p21-activated protein kinase (Pak) and SPS1 families [1-3]. In contrast to Pak family members, SPS1 family members do not bind and are not activated by GTP-bound p21Rac and Cdc42. We recently placed a member of the SPS1 family, called Misshapen (Msn), genetically upstream of the c-Jun amino-terminal (JNK) mitogen-activated protein (MAP) kinase module in Drosophila [4]. The failure to activate JNK in Drosophila leads to embryonic lethality due to the failure of these embryos to stimulate dorsal closure [5-8]. Msn probably functions as a MAP kinase kinase kinase kinase in Drosophila, activating the JNK pathway via an, as yet, undefined MAP kinase kinase kinase. We have identified a Drosophila TNF-receptor-associated factor, DTRAF1, by screening for Msn-interacting proteins using the yeast two-hybrid system. In contrast to the mammalian TRAFs that have been shown to activate JNK, DTRAF1 lacks an amino-terminal 'Ring-finger' domain, and overexpression of a truncated DTRAF1, consisting of only its TRAF domain, activates JNK. We also identified another DTRAF, DTRAF2, that contains an amino-terminal Ring-finger domain. Msn specifically binds the TRAF domain of DTRAF1 but not that of DTRAF2. In Drosophila, DTRAF1 is thus a good candidate for an upstream molecule that regulates the JNK pathway by interacting with, and activating, Msn. Consistent with this idea, expression of a dominant-negative Msn mutant protein blocks the activation of JNK by DTRAF1. Furthermore, coexpression of Msn with DTRAF1 leads to the synergistic activation of JNK. We have extended some of these observations to the mammalian homolog of Msn, Nck-interacting kinase (NIK), suggesting that TRAFs also play a critical role in regulating Ste20 kinases in mammals
— id: 6050, year: 1999, vol: 9, page: 101, stat: Journal Article,

A conserved blueprint for the eye?
Treisman JE
1999 Oct;21(10):843-850, Bioessays
Although the eyes of all organisms have a common function, visual perception, their structures and developmental mechanisms are quite diverse. Recent research on eye development in Drosophila has identified a set of putative transcription factors required for the earliest step of eye development, specification of the field of cells that will give rise to the eye. These factors appear to act in a hierarchy, although cross-regulation may amplify the eye fate decision or promote progression to the next step. Surprisingly, homologous proteins are also involved in vertebrate eye development, suggesting that this regulatory network was present in a primitive common ancestor and that it has been adapted to control visual organ formation in multiple species. The identification of genes acting upstream and downstream of these transcription factors will contribute to our understanding of the establishment of a developmental field, as well as of the divergence of regulatory pathways controlling the formation of eye structures.
— id: 11959, year: 1999, vol: 21, page: 843, stat: Journal Article,

decapentaplegic and wingless are regulated by eyes absent and eyegone and interact to direct the pattern of retinal differentiation in the eye disc
Hazelett DJ; Bourouis M; Walldorf U; Treisman JE
1998 Sep;125(18):3741-3751, Development
Signaling by the secreted hedgehog, decapentaplegic and wingless proteins organizes the pattern of photoreceptor differentiation within the Drosophila eye imaginal disc; hedgehog and decapentaplegic are required for differentiation to initiate at the posterior margin and progress across the disc, while wingless prevents it from initiating at the lateral margins. Our analysis of these interactions has shown that initiation requires both the presence of decapentaplegic and the absence of wingless, which inhibits photoreceptor differentiation downstream of the reception of the decapentaplegic signal. However, wingless is unable to inhibit differentiation driven by activation of the epidermal growth factor receptor pathway. The effect of wingless is subject to regional variations in control, as the anterior margin of the disc is insensitive to wingless inhibition. The eyes absent and eyegone genes encode members of a group of nuclear proteins required to specify the fate of the eye imaginal disc. We show that both eyes absent and eyegone are required for normal activation of decapentaplegic expression at the posterior and lateral margins of the disc, and repression of wingless expression in presumptive retinal tissue. The requirement for eyegone can be alleviated by inhibition of the wingless signaling pathway, suggesting that eyegone promotes eye development primarily by repressing wingless. These results provide a link between the early specification and later differentiation of the eye disc
— id: 7594, year: 1998, vol: 125, page: 3741, stat: Journal Article,

The Drosophila Ste20-related kinase misshapen is required for embryonic dorsal closure and acts through a JNK MAPK module on an evolutionarily conserved signaling pathway
Su YC; Treisman JE; Skolnik EY
1998 Aug 1;12(15):2371-2380, Genes & development
Dorsal closure in the Drosophila embryo occurs during the later stages of embryogenesis and involves changes in cell shape leading to the juxtaposition and subsequent adherence of the lateral epidermal primordia over the amnioserosa. Dorsal closure requires the activation of a conserved c-jun amino-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) module, as it is blocked by null mutations in JNK kinase [hemipterous (hep)] and JNK [basket (bsk)]. Drosophila JNK (DJNK) functions by phosphorylating and activating DJun, which in turn induces the transcription of decapentaplegic (dpp). We provide biochemical and genetic evidence that a Ste20-related kinase, misshapen (msn), functions upstream of hep and bsk to stimulate dorsal closure in the Drosophila embryo. Mammalian (NCK-interacting kinase [NIK]) and Caenorhabditis elegans (mig-15) homologs of msn have been identified; mig-15 is necessary for several developmental processes in C. elegans. These data suggest that msn, mig-15, and NIK are components of a signaling pathway that is conserved among flies, worms, and mammals to control developmentally regulated pathways
— id: 7813, year: 1998, vol: 12, page: 2371, stat: Journal Article,

Eye development in Drosophila: formation of the eye field and control of differentiation
Treisman JE; Heberlein U
1998 ;39:119-158, Current topics in developmental biology
— id: 7829, year: 1998, vol: 39, page: 119, stat: Journal Article,

eyelid antagonizes wingless signaling during Drosophila development and has homology to the Bright family of DNA-binding proteins
Treisman JE; Luk A; Rubin GM; Heberlein U
1997 Aug 1;11(15):1949-1962, Genes & development
In Drosophila, pattern formation at multiple stages of embryonic and imaginal development depends on the same intercellular signaling pathways. We have identified a novel gene, eyelid (eld), which is required for embryonic segmentation, development of the notum and wing margin, and photoreceptor differentiation. In these tissues, eld mutations have effects opposite to those caused by wingless (wg) mutations. eld encodes a widely expressed nuclear protein with a region homologous to a novel family of DNA-binding domains. Based on this homology and on the phenotypic analysis, we suggest that Eld could act as a transcription factor antagonistic to the Wg pathway
— id: 7274, year: 1997, vol: 11, page: 1949, stat: Journal Article,