| Pattern formation in the Drosophila visual system
Jessica E. Treisman Ph.D.
Associate Professor
Department of Cell Biology (Skirball) Skirball Institute Program of Developmental Genetics |
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| Research Summary |
The Drosophila eye is a highly ordered structure consisting of 800 identical ommatidia; their arrangement and their connections to the brain must be very precise so that the fly has an accurate view of the world. We are studying the mechanism by which this order arises during development. Differentiation of cells within the eye primordium, the eye imaginal disc, is a progressive process that moves across the disc from posterior to anterior. The movement of this developmental wave is organized by signaling molecules from gene families also present in other organisms. Positive signals inducing differentiation are provided by the Hedgehog and Decapentaplegic (TGF-beta family) proteins, and a negative signal restricting where differentiation can occur comes from the Wingless (Wnt family) protein. We are taking a genetic approach to identify other molecules involved in establishing the early pattern of differentiation in the eye, or in specifying the field of cells that gives rise to the eye. One example, the act up gene, has shown us that changes in cell shape are required to control the spread of the Hedgehog protein and coordinate photoreceptor differentiation. We have also identified mutations in the hyperplastic discs gene, which encodes a ubiquitin protein ligase required to prevent the premature expression of Hedgehog, and the sightless gene, which encodes a transmembrane protein that appears to modify the Hedgehog protein by adding an essential fatty acid. We are continuing to screen for additional genes.
We are also studying the effects of general transcriptional regulators on the transmission of specific developmental signals. The osa gene encodes a novel, non-sequence-specific DNA-binding protein with highly conserved human and mouse homologues. Osa associates with the Brahma chromatin remodeling complex, the Drosophila homologue of the yeast SWI/SNF complex. Osa also acts downstream of the Wingless signal to repress the expression of Wingless target genes. Osa appears to maintain a repressive chromatin structure on the promoters of such genes that can be overcome by Wingless signaling. We have also identified mutations in two components of the mediator complex, TRAP240 and TRAP230. Unlike core components of the complex, these proteins are not required for cell growth or proliferation. However, mutations in both genes have identical and specific developmental phenotypes, suggesting that these proteins act to transmit signals from several pathways.
Finally, we are studying the pattern of connections formed by the photoreceptor axons; these connections recreate a map of the visual field in the brain. We are screening for mutations that affect the ability of these axons to terminate at the correct position. We have found that the protein tyrosine phosphatase Dlar is specifically required for the UV-sensitive photoreceptor R7 to reach its target site. |
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| Related Images |
Image 1 | Scanning electron micrograph of a Drosophila eye (left) and a larval eye disc stained with an antibody to recognize differentiating photoreceptors in brown and a dpp-lacZ reporter to mark the morphogenetic furrow in blue (right). | | |
| Research Information |
Research Interests | Pattern formation in the Drosophila visual system
| Research Keywords | Drosophila, visual system, axon guidance, chromatin, mediator, Wingless, Hedgehog |
