Cynthia Ann Loomis, M.D., Ph.D.

Nerve-derived sonic hedgehog defines a niche for hair follicle stem cells capable of becoming epidermal stem cells
Brownell, Isaac; Guevara, Elizabeth; Bai, C Brian; Loomis, Cynthia A; Joyner, Alexandra L
2011 May 6;8(5):552-565, Cell Stem Cell
In adult skin, stem cells in the hair follicle bulge cyclically regenerate the follicle, whereas a distinct stem cell population maintains the epidermis. The degree to which all bulge cells have equal regenerative potential is not known. We found that Sonic hedgehog (Shh) from neurons signals to a population of cells in the telogen bulge marked by the Hedgehog response gene Gli1. Gli1-expressing bulge cells function as multipotent stem cells in their native environment and repeatedly regenerate the anagen follicle. Shh-responding perineural bulge cells incorporate into healing skin wounds where, notably, they can change their lineage into epidermal stem cells. The perineural niche (including Shh) is dispensable for follicle contributions to acute wound healing and skin homeostasis, but is necessary to maintain bulge cells capable of becoming epidermal stem cells. Thus, nerves cultivate a microenvironment where Shh creates a molecularly and phenotypically distinct population of hair follicle stem cells
— id: 133414, year: 2011, vol: 8, page: 552, stat: Journal Article,

The Hedgehog response gene Gli1 marks multipotent stem cells in the telogen bulge
Brownell, Isaac; Loomis, Cynthia A.; Joyner, Alexandra L.
2010 SEP ;130(4):S88-S88, Journal of investigative dermatology
— id: 113755, year: 2010, vol: 130, page: S88, stat: Journal Article,

ADAM12: a potential target for the treatment of chronic wounds
Harsha, Asheesh; Stojadinovic, Olivera; Brem, Harold; Sehara-Fujisawa, Atsuko; Wewer, Ulla; Loomis, Cynthia A; Blobel, Carl P; Tomic-Canic, Marjana
2008 Aug;86(8):961-969, Journal of Molecular Medicine (Berlin)
Wound healing is a complex process involving multiple cellular events, including cell proliferation, migration, and tissue remodeling. A disintegrin and metalloprotease 12 (ADAM12) is a membrane-anchored metalloprotease, which has been implicated in activation-inactivation of growth factors that play an important role in wound healing, including heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) and insulin growth factor (IGF) binding proteins. Here, we report that expression of ADAM12 is fivefold upregulated in the nonhealing edge of chronic ulcers compared to healthy skin, based on microarrays of biopsies taken from five patients and from healthy controls (p = 0.013). The increase in ADAM12 expression in chronic ulcers was confirmed by quantitative real-time polymerase chain reaction (RT-PCR). Moreover, immunohistochemical analysis demonstrated a pronounced increase in the membranous and intracellular signal for ADAM12 in the epidermis of chronic wounds compared to healthy skin. These findings, coupled with our previous observations that lack of keratinocyte migration contributes to the pathogenesis of chronic ulcers, prompted us to evaluate how the absence of ADAM12 affects the migration of mouse keratinocytes. Skin explants from newborn ADAM12(-/-) or wild-type (WT) mice were used to quantify keratinocyte migration out of the explants over a period of 7 days. We found a statistically significant increase in the migration of ADAM12(-/-) keratinocytes compared to WT control (p = 0.0014) samples. Taken together, the upregulation of ADAM12 in chronic wounds and the increased migration of keratinocytes in the absence of ADAM12 suggest that ADAM12 is an important mediator of wound healing. We hypothesize that increased expression of ADAM12 in chronic wounds impairs wound healing through the inhibition of keratinocyte migration and that topical ADAM12 inhibitors may therefore prove useful for the treatment of chronic wounds
— id: 79473, year: 2008, vol: 86, page: 961, stat: Journal Article,

ADAM12: a potential target for treatment of chronic wounds
Harsha, A; Stojadinovic, O; Loomis, CA; Blobel, CP; Tomic-Canic, M
2007 APR ;127(2):S37-S37, Journal of investigative dermatology
— id: 71618, year: 2007, vol: 127, page: S37, stat: Journal Article,

STAT3 signaling and the hyper-IgE syndrome
Levy, David E; Loomis, Cynthia A
2007 Oct 18;357(16):1655-1658, New England journal of medicine
— id: 93454, year: 2007, vol: 357, page: 1655, stat: Journal Article,

The homeoprotein engrailed 1 has pleiotropic functions in calvarial intramembranous bone formation and remodeling
Deckelbaum, Ron A; Majithia, Amit; Booker, Thomas; Henderson, Janet E; Loomis, Cynthia A
2006 Jan;133(1):63-74, Development
The membranous bones of the mammalian skull vault arise from discrete condensations of neural crest- and mesodermally-derived cells. Recently, a number of homeodomain transcription factors have been identified as critical regulators of this process. Here, we show that the homeoprotein engrailed 1 (EN1) is expressed during embryonic and perinatal craniofacial bone development, where it localizes to the skeletogenic mesenchyme, and, subsequently, to calvarial osteoblasts and osteoprogenitors. Mice lacking En1 exhibit generalized calvarial bone hypoplasia and persistent widening of the sutural joints. A reduction in calvarial membranous bone deposition and mineralization (osteopenia) is coupled to enhanced osteolytic resorption in En1 mutants. Consistent with these observations, expression of established osteoblast differentiation markers reveals that En1 function is required for both early and late phases of calvarial osteogenesis. Further analysis shows that EN1 regulates FGF signaling in calvarial osteoblasts. Moreover, EN1 indirectly influences calvarial osteoclast recruitment and bone resorption by regulating the expression of receptor activator of NFkappaB ligand (RANKL) in osteoblasts. Thus, during intramembranous bone formation, EN1 acts both cell autonomously and non-cell autonomously. In summary, this study identifies EN1 as a novel modulator of calvarial osteoblast differentiation and proliferation, processes that must be exquisitely balanced to ensure proper skull vault formation
— id: 64195, year: 2006, vol: 133, page: 63, stat: Journal Article,

Conditional ablation of epidermal En1 reveals a postnatal regulatory role
Pechar, D; Kraus, P; Loomis, CA
2006 APR ;126(1):98-98, Journal of investigative dermatology
— id: 70334, year: 2006, vol: 126, page: 98, stat: Journal Article,

Developmental analysis of nail development
Pechar, D; Zhao, Z; Loomis, CA
2004 MAR ;122(3):A109-A109, Journal of investigative dermatology
— id: 46580, year: 2004, vol: 122, page: A109, stat: Journal Article,

Detailed characterization of eccrine gland development
Sanchez, L; Tong, C; Loomis, CA
2004 MAR ;122(3):A112-A112, Journal of investigative dermatology
— id: 46583, year: 2004, vol: 122, page: A112, stat: Journal Article,

Fate map of mouse ventral limb ectoderm and the apical ectodermal ridge
Guo, Qiuxia; Loomis, Cynthia; Joyner, Alexandra L
2003 Dec 1;264(1):166-178, Developmental biology (Orlando)
The apical ectodermal ridge (AER) is a critical signaling center at the tip of the limb that promotes outgrowth. In mouse, formation of the AER involves a gradual restriction of AER gene expression from a broad ventral preAER domain to the tip of the limb, as well as progressive thickening of cells to form a multilayered epithelium. The AER is visible from embryonic day 10.5 to 13.5 (E10.5-E13.5) in the mouse forelimb. Previous short-term fate mapping studies indicated that, once a cell is incorporated into the AER, its descendents remain within the AER. In addition, some preAER cells appear to become incorporated into the ventral ectoderm. In the present study, we used an inducible CreER/loxP fate mapping approach in mouse to examine the long-term contribution of preAER cells to limb ventral ectoderm, as well as the ultimate fate of the mature AER cells. We used a CreER transgene that contains Msx2 regulatory sequences specific to the developing AER, and demonstrate by marking preAER cells that, at stage 2 of mouse limb bud development, the majority of the ventral ectoderm that protrudes from the body wall later covers only the paw. Furthermore, when Msx2-CreER-expressing preAER cells are marked after the onset of preAER gene expression, a similar domain of paw ventral ectoderm is marked at E16.5, in addition to the AER. Strikingly, mapping the long-term fate of cells that form the mature AER showed that, although this structure is indeed a distinct compartment, AER-derived cells are gradually lost after E12.5 and no cells remain by birth. A distinct dorsal/ventral border nevertheless is maintained in the ectoderm of the paw, with the distal-most border being located at the edge of the nail bed. These studies have uncovered new aspects of the cellular mechanisms involved in AER formation and in partitioning the ventral ectoderm in mouse limb
— id: 44888, year: 2003, vol: 264, page: 166, stat: Journal Article,

What syndrome is this? Nail-patella syndrome
Buddin, Deidre; Loomis, Cynthia; Shwayder, Tor; Chang, Mary Wu
2002 Sep-Oct;19(5):454-456, Pediatric dermatology
— id: 39389, year: 2002, vol: 19, page: 454, stat: Journal Article,

PTCH (patched) and XPA genes in radiation-induced basal cell carcinomas
Burns FJ; Shore RE; Roy N; Loomis C; Zhao P
Radiation and Homeostasis : proceedings of the International Symposium of Radiation and Homeostasis, held in Kyoto, Japan, 13-16 July 2001 Amsterdam ; Boston : Elsevier, 2002,
— id: 3100, year: 2002, vol: , page: 175, stat: Chapter,

Hair vs. eccrine gland: Timing and competition of skin appendage specification on the limb
Loomis, C; Tong, C; Kraus, P
2002 JUL ;119(1):290-290, Journal of investigative dermatology
— id: 55288, year: 2002, vol: 119, page: 290, stat: Journal Article,

Fibroma induction in rat skin following single or multiple doses of 1.0 GeV/nucleon 56Fe ions from the Brookhaven Alternating Gradient Synchrotron (AGS)
Burns FJ; Zhao P; Xu G; Roy N; Loomis C
2001 ;17 Suppl 1(8):194-195, Physica medica
Rat skin was exposed to the plateau region of the 1.0 GeV/nucleon 56Fe beam at the Brookhaven AGS. Rats were irradiated or not with single of split doses of 56Fe or argon; some 56Fe-exposed rats were fed 250 ppm retinyl acetate continuously in the lab chow beginning 1 week before irradiation. All lesions were noted, photographed and identified for eventual histological diagnosis. The preponderance of the tumors so far are fibromas. The data show that single doses of 56Fe ions are 2 or 3 fold more effective than argon in producing tumors at 4.5 Gy but are about equally effective at 3.0 Gy and 9.0 Gy. The presence of 250 ppm retinyl acetate in the lab chow reduced the incidence of tumors by about 50-60% in comparison to groups exposed only to the radiation. These are preliminary findings based on only about one-fourth the eventual number of tumors expected
— id: 32228, year: 2001, vol: 17 Suppl 1, page: 194, stat: Journal Article,

Some distal limb structures develop in mice lacking Sonic hedgehog signaling
Kraus P; Fraidenraich D; Loomis CA
2001 Jan;100(1):45-58, Mechanisms of development
Patterning of the limb is coordinated by the complex interplay of three signaling regions: the apical ectodermal ridge (AER), the zone of polarizing activity (ZPA), and the non-ridge limb ectoderm. Complex feedback loops exist between Shh in the ZPA, Bmps and their antagonists in the adjacent mesenchyme, Wnt7a in the dorsal ectoderm and Fgfs in the AER. In contrast to the previously reported complete absence of digits in Shh(-/-) mice, we show that one morphologically distinct digit, with a well-delineated nail and phalanges, forms in Shh(-/-) hindlimbs, while intermediate structures are severely truncated and fused. The presence of distal autopod elements is consistent with weak expression of Hoxd13 in Shh(-/-) hindlimbs. Shh(-/-) forelimbs in contrast have one distal cartilage element, a less-well differentiated nail and fused intermediate bones. Interestingly, Ihh is expressed at the tip of Shh mutant limbs and could account for formation of distal structures. In contrast to previous studies we also demonstrate that Shh signaling is required for maintenance of normal Fgf8 expression, since expression of Fgf8, unlike some other AER marker genes, is rapidly lost from anterior to posterior after E10.5, with only a small domain of Fgf8 expression remaining posteriorly. Furthermore, loss of expanded Fgf8 expression is paralleled by a collapse of the handplate. Our data show that development of most intermediate elements of the hindlimb skeleton are Shh-dependent, and that Shh signaling is required for anterior-posterior expansion of the AER in both limbs and for the subsequent branching of zeugopod and autopod elements. Finally, we show that Shh is also required for outgrowth of the limb ectoderm and thus for the formation of a distinct limb compartment
— id: 16621, year: 2001, vol: 100, page: 45, stat: Journal Article,

Engrailed1 is critical for repression of nail-type differentiation in mouse
Kraus, P; Tong, CX; Loomis, CA; Perelman, RO
2001 JUL 1 ;235(1):195-195, Developmental biology (Orlando)
— id: 54997, year: 2001, vol: 235, page: 195, 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,

Development and morphogenesis of the skin
Loomis CA
2001 ;17(2):183-210, Advances in dermatology
— id: 34998, year: 2001, vol: 17, page: 183, stat: Journal Article,

Keratosis pilaris and variants
Schmults CD; Loomis C
Current dermatologic diagnosis & treatment Philadelphia : Lippincott Williams & Wilkins, 2001,
— id: 3714, year: 2001, vol: , page: 96, stat: Chapter,

Engrailed-1 in postnatal skin homeostasis and hair cycling
Birge, M B; Tong, C; Kraus, P; Loomis, C A
2000 May 10-14;114(4):824-824, Journal of investigative dermatology
— id: 15816, year: 2000, vol: 114, page: 824, stat: Journal Article,

Two lineage boundaries coordinate vertebrate apical ectodermal ridge formation
Kimmel RA; Turnbull DH; Blanquet V; Wurst W; Loomis CA; Joyner AL
2000 Jun 1;14(11):1377-1389, Genes & development
Proximal-distal outgrowth of the vertebrate limb bud is regulated by the apical ectodermal ridge (AER), which forms at an invariant position along the dorsal-ventral (D/V) axis of the embryo. We have studied the genetic and cellular events that regulate AER formation in the mouse. In contrast to implications from previous studies in chick, we identified two distinct lineage boundaries in mouse ectoderm prior to limb bud outgrowth using a Cre/loxP-based fate-mapping approach and a novel retroviral cell-labeling technique. One border is transient and at the limit of expression of the ventral gene En1, which corresponds to the D/V midline of the AER, and the second border corresponds to the dorsal AER margin. Labeling of AER precursors using an inducible Cre showed that not all cells that initially express AER genes form the AER, indicating that signaling is required to maintain an AER phenotype. Misexpression of En1 at moderate levels specifically in the dorsal AER of transgenic mice was found to produce dorsally shifted AER fragments, whereas high levels of En1 abolished AER formation. In both cases, the dorsal gene Wnt7a was repressed in cells adjacent to the En1-expressing cells, demonstrating that signaling regulated by EN1 occurs across the D/V border. Finally, fate mapping of AER domains in these mutants showed that En1 plays a part in positioning and maintaining the two lineage borders
— id: 11671, year: 2000, vol: 14, page: 1377, stat: Journal Article,

Two lineage boundaries and EN1 coordinate AER formation
Kimmel, RA; Turnbull, DH; Blanquet, V; Wurst, W; Loomis, CA; Joyner, AL
2000 JUN 1 ;222(1):227-227, Developmental biology (Orlando)
— id: 54559, year: 2000, vol: 222, page: 227, stat: Journal Article,

Distal most limb structures develop despite absence of Shh signaling in mouse
Kraus, P; Fraidenraich, D; Basilico, C; Loomis, CA
2000 JUN 1 ;222(1):267-267, Developmental biology (Orlando)
— id: 54562, year: 2000, vol: 222, page: 267, stat: Journal Article,

Engrailed-1 (En1) expression by the dermal papilla affects hair size in mouse skin
Birge, MB; Tong, CX; Mohan, S; Perone, J; Loomis, CA
1999 APR ;112(4):524-524, Journal of investigative dermatology
— id: 54078, year: 1999, vol: 112, page: 524, stat: Journal Article,

En1 plays multiple roles in vertebrate limb development
Kimmel, R; Loomis, C; Losos, K; Turnbull, D; Joyner, A
1999 JUN 1 ;210(1):228-228, Developmental biology (Orlando)
— id: 54019, year: 1999, vol: 210, page: 228, stat: Journal Article,

Architectural organization of filiform papillae in normal and black hairy tongue epithelium: dissection of differentiation pathways in a complex human epithelium according to their patterns of keratin expression
Manabe M; Lim HW; Winzer M; Loomis CA
1999 Feb;135(2):177-181, Archives of dermatology
BACKGROUND: An inadequate understanding of the complex morphologic characteristics of human filiform papillae has hampered the histopathological characterization of disorders affecting tongue keratinization. To better define the 3-dimensional cytoarchitecture of tongue epithelium, we performed detailed immunohistochemical analyses of normal and black hairy tongue tissues using a panel of antikeratin antibodies. OBSERVATIONS: The dome-shaped base of the human filiform papilla (primary papilla) is surmounted by 3 to 8 elongated structures (secondary papillae). These secondary papillae are composed of a central column of epithelial cells expressing hair-type keratins and an outer rim of cells expressing skin-type keratins. The epithelium overlying the primary papillae and between the individual primary papillae express esophageal-type keratins. In black hairy tongue disease, there is a marked retention of secondary papillary cells expressing hair-type keratins. CONCLUSIONS: Using a panel of antikeratin probes, we define the precise topographical localization of cell populations undergoing 3 distinct differentiation programs in dorsal tongue epithelium. Comparative analyses of black hairy tongue specimens indicate that defective desquamation of the cells in the central column of filiform papillae results in the formation of highly elongated, cornified spines or, 'hairs'--the hallmark of this disease
— id: 7399, year: 1999, vol: 135, page: 177, stat: Journal Article,

Drosophila engrailed can substitute for mouse Engrailed1 function in mid-hindbrain, but not limb development
Hanks MC; Loomis CA; Harris E; Tong CX; Anson-Cartwright L; Auerbach A; Joyner A
1998 Nov;125(22):4521-4530, Development
The Engrailed-1 gene, En1, a murine homologue of the Drosophila homeobox gene engrailed (en), is required for midbrain and cerebellum development and dorsal/ventral patterning of the limbs. In Drosophila, en is involved in regulating a number of key patterning processes including segmentation of the epidermis. An important question is whether, during evolution, the biochemical properties of En proteins have been conserved, revealing a common underlying molecular mechanism to their diverse developmental activities. To address this question, we have replaced the coding sequences of En1 with Drosophila en. Mice expressing Drosophila en in place of En1 have a near complete rescue of the lethal En1 mutant brain defect and most skeletal abnormalities. In contrast, expression of Drosophila en in the embryonic limbs of En1 mutants does not lead to repression of Wnt7a in the embryonic ventral ectoderm or full rescue of the embryonic dorsal/ventral patterning defects. Furthermore, neither En2 nor en rescue the postnatal limb abnormalities that develop in rare En1 null mutants that survive. These studies demonstrate that the biochemical activity utilized in mouse to mediate brain development has been retained by Engrailed proteins across the phyla, and indicate that during evolution vertebrate En proteins have acquired two unique functions during embryonic and postnatal limb development and that only En1 can function postnatally
— id: 7339, year: 1998, vol: 125, page: 4521, stat: Journal Article,

Analysis of the genetic pathway leading to formation of ectopic apical ectodermal ridges in mouse Engrailed-1 mutant limbs
Loomis CA; Kimmel RA; Tong CX; Michaud J; Joyner AL
1998 Mar;125(6):1137-1148, Development
The apical ectodermal ridge (AER), a rim of thickened ectodermal cells at the interface between the dorsal and ventral domains of the limb bud, is required for limb outgrowth and patterning. We have previously shown that the limbs of En1 mutant mice display dorsal-ventral and proximal-distal abnormalities, the latter being reflected in the appearance of a broadened AER and formation of ectopic ventral digits. A detailed genetic analysis of wild-type, En1 and Wnt7a mutant limb buds during AER development has delineated a role for En1 in normal AER formation. Our studies support previous suggestions that AER maturation involves the compression of an early broad ventral domain of limb ectoderm into a narrow rim at the tip and further show that En1 plays a critical role in the compaction phase. Loss of En1 leads to a delay in the distal shift and stratification of cells in the ventral half of the AER. At later stages, this often leads to development of a secondary ventral AER, which can promote formation of an ectopic digit. The second AER forms at the juxtaposition of the ventral border of the broadened mutant AER and the distal border of an ectopic Lmx1b expression domain. Analysis of En1/Wnt7a double mutants demonstrates that the dorsalizing gene Wnt7a is required for the formation of the ectopic AERs in En1 mutants and for ectopic expression of Lmx1b in the ventral mesenchyme. We suggest a model whereby, in En1 mutants, ectopic ventral Wnt7a and/or Lmx1b expression leads to the transformation of ventral cells in the broadened AER to a more dorsal phenotype. This leads to induction of a second zone of compaction ventrally, which in some cases goes on to form an autonomous secondary AER
— id: 7664, year: 1998, vol: 125, page: 1137, stat: Journal Article,

Engrailed-1 expression and regulatory role during skin appendage development
Mohan, S; Tong, CX; Perone, J; Chubak, B; Kimmel, R; Joyner, AL; Loomis, CA
1998 APR ;110(4):603-603, Journal of investigative dermatology
— id: 53525, year: 1998, vol: 110, page: 603, stat: Journal Article,

Role of En1 in vertebrate limb patterning
Kimmel, RA; Loomis, CA; Joyner, AL
1997 ;186(2):B230-B230, Developmental biology (Orlando)
— id: 104601, year: 1997, vol: 186, page: B230, stat: Journal Article,

American Academy of Dermatology 1997 Awards for Young Investigators in Dermatology. The role of Engrailed-1 in limb development and skin patterning
Loomis C
1997 Nov;37(5 Pt 1):774-775, Journal of the American Academy of Dermatology
— id: 12225, year: 1997, vol: 37, page: 774, stat: Journal Article,

Linear hypopigmentation and hyperpigmentation, including mosaicism
Loomis CA
1997 Mar;16(1):44-53, Seminars in cutaneous medicine & surgery
Linear streaks of hypopigmentation or hyperpigmentation along Blaschko's lines are currently grouped under the names hypomelanosis of Ito (HI) and linear and whorled hypermelanosis (LWH). Recent studies have suggested that these linear pigmentary anomalies reflect underlying genetic mosaicism. Mosaic individuals are composed of two or more genetically distinct cell populations, a normal and an abnormal population. In HI and LWH, the types of genetic defects that are detectable in the abnormal population are highly variable, including tetraploidy, partial or complete trisomies, translocations, and point mutations. These results, together with recent studies indicating the incidence of extracutaneous anomalies is lower in HI but higher in LWH than previously estimated, have important clinical implications. The need for a revised nomenclature as well as possible modifications in current recommendations for patient management are discussed
— id: 7205, year: 1997, vol: 16, page: 44, stat: Journal Article,

Engrailed-1 (En1) plays multiple roles in patterning of the distal limb and development of the overlying skin
Loomis, CA; Tong, XC; Zeitler, E; Kimmel, RA; Paulson, M; Hanks, M; Joyner, AL
1997 APR ;108(4):241-241, Journal of investigative dermatology
— id: 53217, year: 1997, vol: 108, page: 241, stat: Journal Article,

The mouse Engrailed-1 gene and ventral limb patterning
Loomis CA; Harris E; Michaud J; Wurst W; Hanks M; Joyner AL
1996 Jul 25;382(6589):360-363, Nature
During vertebrate limb development, positional information must be specified along three distinct axes. Although much progress has been made in our understanding of the molecular interactions involved in anterior-posterior and proximal-distal limb patterning, less is known about dorsal-ventral patterning. The genes Wnt-7a and Lmx-1, which are expressed in dorsal limb ectoderm and mesoderm, respectively, are thought to be important regulators of dorsal limb differentiation. Whether a complementary set of molecules controls ventral limb development has not been clear. Here we report that Engrailed-1, a homeodomain-containing transcription factor expressed in embryonic ventral limb ectoderm, is essential for ventral limb patterning. Loss of Engrailed-1 function in mice results in dorsal transformations of ventral paw structures, and in subtle alterations along the proximal-distal limb axis. Engrailed-1 seems to act in part by repressing dorsal differentiation induced by Wnt-7a, and is essential for proper formation of the apical ectodermal ridge
— id: 56881, year: 1996, vol: 382, page: 360, stat: Journal Article,

Cutaneous findings in mosaicism and chimerism
Loomis CA; Orlow SJ
1996 ;3:87-92, Current opinion in dermatology
— id: 48978, year: 1996, vol: 3, page: 87, stat: Journal Article,

The role of Engrailed-1 in epidermal appendage formation and skin patterning
Loomis, CA; Michaud, J; Hanks, M; Joyner, AL
1996 APR ;106(4):171-171, Journal of investigative dermatology
— id: 52997, year: 1996, vol: 106, page: 171, stat: Journal Article,

Trichohyalin expression in skin tumors: retrieval of trichohyalin antigenicity in tissues by microwave irradiation
Manabe M; Yaguchi H; Iqbal Butt K; O'Guin WM; Loomis CA; Sung TT; Ogawa H
1996 May;35(5):325-329, International journal of dermatology
BACKGROUND. The antitrichohyalin antibody AE 15 is effective for identifying the cell lineage that undergoes the pathway of inner root sheath-type differentiation. Unfortunately, the AE 15 does not react with trichohyalin in tissue that is formalin-fixed and embedded in paraffin according to routine procedures. METHODS. We attempted to retrieve the trichohyalin antigenicity in formalin-fixed, paraffin-embedded biopsy specimens that included normal skin as well as skin tumors such as trichofolliculoma and pilotricoma. RESULTS. We found that the use of a metal solution in combination with microwave oven heating improves the trichohyalin immunoreactivity substantially. Further, trichohyalin was found to be expressed not only in the secondary hair structure in trichofolliculoma but also in a certain cell lineage that differentiates to squamoid cells in pilomatricoma. CONCLUSIONS. Our findings established that surgical specimens processed under routine procedures can be successfully investigated with AE 15 using the microwave irradiation method. Studies of epidermal diseases expressing trichohyalin should provide valuable insights into our understanding the functional significance of trichohyalin during abnormal keratinization
— id: 16622, year: 1996, vol: 35, page: 325, stat: Journal Article,

EXPRESSION OF A TRICHOHYALIN GENE UNDER THE CONTROL OF AN RSV PROMOTOR IN HUMAN EPIDERMAL-KERATINOCYTES
LOOMIS, C; OGUIN, WM
1995 APR ;104(4):641-641, Journal of investigative dermatology
— id: 87383, year: 1995, vol: 104, page: 641, stat: Journal Article,

THE CLONING AND CHARACTERIZATION OF THE GENE ENCODING MURINE TRICHOHYALIN
OGUIN, WM; SUN, TT; LOOMIS, CA
1994 APR ;102(4):607-607, Journal of investigative dermatology
— id: 52347, year: 1994, vol: 102, page: 607, stat: Journal Article,

Characterization of a keratinocyte-specific extracellular epitope of desmoglein. Implications for desmoglein heterogeneity and function
Loomis CA; Kolega J; Manabe M; Sun TT
1992 Aug 15;267(23):16676-16684, Journal of biological chemistry
Despite the presumed importance of desmoglein, a 160-kDa glycoprotein, in desmosome formation and its possible involvement in certain blistering skin diseases, the precise location and function of this protein have not yet been firmly established. We describe here the characterization of a new monoclonal antibody, AE23, against an extracellular epitope of desmoglein. Both the AE23 epitope and another epitope, defined by the previously characterized DG3.4 antibody, reside on a 160-kDa human epidermal desmoglein as evidenced by their identical solubility profile, their coexistence in a 130-kDa desmoglein degradative product, their coadsorption by an AE23 immunoaffinity column, and the identical changes in the two antigens' electrophoretic mobility after air oxidation and deglycosylation. The AE23 epitope is resistant to various endoglycosidases, suggesting that sugar moieties are not involved. Characterization of several proteolytic fragments of this epidermal desmoglein enabled us to map the DG3.4 epitope to a 96-kDa intracellular domain and the AE23 epitope to an extracellular domain flanked by the plasma membrane and the distal N-glycosylation site(s). However, these two epitopes do not always coexist on the same desmoglein molecule. For example, tissue surveys showed that although the DG3.4 epitope is present in the desmogleins of all epithelial cell types, the AE23 epitope is limited to normal keratinocytes. Moreover, electron microscopic localization data indicate that whereas the DG3.4 epitope is detected in the submembranous plaques of desmosomes, the AE23 epitope is present in the intercellular space of both desmosomal and nondesmosomal areas. These results raise the possibility that there exist several biochemically closely related isoforms of desmoglein, one (AE23+/DG3.4+) restricted to epidermal desmosomes, one (AE23+/DG3.4-) uniformly distributed along the keratinocyte cell surface, and another (AE23-/DG3.4+) present in desmosomes of simple epithelia and basal cells of cultured keratinocytes. The uniform distribution of at least one desmoglein-related antigen in the intercellular space of keratinocytes coupled with the realization that different isoforms of desmogleins form a subfamily of cadherins suggest that desmoglein(s) may play a more general role in keratinocyte adhesion than previously appreciated
— id: 13478, year: 1992, vol: 267, page: 16676, stat: Journal Article,

REDUCED LEVEL OF DESMOGLEIN IN BASAL-CELL CARCINOMA AND FOLLICULOCENTRIC BASALOID PROLIFERATION
MEHREL, T; MANABE, M; WHITE, W; LESHIN, B; LOOMIS, C; SANCHEZ, M; LAVKER, RM; SUN, TT
1991 APR ;39(2):A527-A527, Clinical research
— id: 51627, year: 1991, vol: 39, page: A527, stat: Journal Article,

REDUCED LEVEL OF DESMOGLEIN IN BASAL-CELL CARCINOMA AND FOLLICULOCENTRIC BASALOID PROLIFERATION
MEHREL, T; MANABE, M; WHITE, W; LESHIN, B; LOOMIS, C; SANCHEZ, M; LAVKER, RM; SUN, TT
1991 APR ;96(4):619-619, Journal of investigative dermatology
— id: 51644, year: 1991, vol: 96, page: 619, stat: Journal Article,

The major pathways of keratinocyte differentiation as defined by keratin expression: an overview
Galvin S; Loomis C; Manabe M; Dhouailly D; Sun TT
1989 ;4:277-299, Advances in dermatology
— id: 10852, year: 1989, vol: 4, page: 277, stat: Journal Article,

Sequence of an expressed human beta-tubulin gene containing ten Alu family members
Lee MG; Loomis C; Cowan NJ
1984 Jul 25;12(14):5823-5836, Nucleic acids research
The complete sequence of a functionally expressed human beta-tubulin gene (5 beta) is presented. The amino acid sequence encoded by this gene constitutes a distinct isotype, differing from a previously described human beta-tubulin sequence at 21 positions throughout the polypeptide chain. The beta-tubulin coding sequence in 5 beta is interrupted by three intervening sequences of 1014, 117 and 4826 nucleotides. The largest of these contains ten members of the Alu family of middle repetitive sequences. Together, these regions account for sixty percent of this intervening sequence. Two of the Alu elements are juxtaposed head to tail, and share the same flanking direct repeat. The ten Alu sequences are substantially divergent, both from each other and from an Alu consensus sequence, and several contain deletions of up to half the entire sequence
— id: 17157, year: 1984, vol: 12, page: 5823, stat: Journal Article,