[ Research Interests ] [ Representative Publications ]

Chen-Ming Fan Adjunct Professor Department of Biology Staff Member Carnegie Institution of Washington B.S. National University of Taiwan Ph.D. Harvard University Postdoctoral University of California, San Francisco

Carnegie Institution of Washington 3520 San Martin Drive Baltimore, MD 21218 U.S.A. Office Telephone: Lab Telephone: Department Fax: Email: Web site: 410.246.3022 410.246-3039 410.243.6311 fan@ciwemb.edu http://www.ciwemb.edu/ labs/fan/index.html Carnegie Institution of Washington

Research Interests The primary interest of my laboratory is to understand the molecular and cellular mechanisms that control vertebrate embryogenesis, with particular focus on identifying signals that direct the development of the musculoskeletal system from a group of mesodermal structures called somites. Under the influence of signals supplied by surrounding tissues, somites differentiate into tissues that give rise to cartilage, dermis, and limb and axial muscle. An in vitro assay system is used to investigate the early events of mouse somite development: the formation of sclerotome (precursor of vertebrae and ribs), dermomyotome (precursor of dermis and limb muscle) and myotome (precursor of axial muscle). In this assay, various tissues isolated from the mouse embryos were co cultured with presomitic mesoderm (precursor to somites) in three-dimensional collagen gels to test their ability to induce specific cell types in the presomitic mesoderm. This system allows the identification of not only the specific inducer tissues but also the cellular mechanisms of these tissue interactions employed to establish the proper somitic pattern. Using this system, Sonic Hedgehog (SHH) expressed in the notochord and floorplate was identified as a diffusible molecule that induces sclerotome differentiation. However, molecular identities of the diffusible signal(s) emanating from neural tube that induces myotome and the contact-dependent signal (s) resides on the surface ectoderm membrane that elicits dermomyotomal fate are not yet defined. The immediate goal of my laboratory is to use various complementary strategies to identify molecules that pattern the dermomyotome and myotome. The identification of all these factors will make it possible to analyze the molecular basis of somite patterning and the differentiation program of muscle, dermis and bone. The long term goals are to identify and study these patterning factors, their signaling pathways and their downstream target genes that control these processes at the molecular level by functional assays. Information contained from these in vitro studies will be utilized to design experiments to assess the function of these molecules in somite differentiation by genetic manipulations in the mouse including homologous recombination and transgenic ectopic expression systems. Representative Publications Martinelli D.C. and Fan C.M. 2007. Gas1 extends the range of Hedgehog action by facilitating its signaling. Genes & Development . 15:1231-1243. Seppala M., Depew M.J., Martinelli D.C., Fan C.M., Sharpe P.T., and Cobourne M.T. 2007. Gas1 is a modifier for holoprosencephaly and genetically interacts with sonic hedgehog. J. Clinical Investigation. 117:1575-1584. Martinelli D.C. and Fan C.M. 2007. The role of Gas1 in embryonic development and its implications for human disease. Cell Cycle . (in press.). Fan CM, Chen AE. (2005). Targeting gene expression in the mouse somite: adenovirus-mediated gene delivery and whole embryo culture. Genesis. 42(2):71-6. Fan CM, Chen AE, Ginty DD. (2005). Protein kinase A signalling via CREB controls myogenesis induced by Wnt proteins. Nature. 433(7023):317-22. Fan CM, Goshu E, Jin H, Lovejoy J, Marion JF, Michaud JL.(2004). Sim2 contributes to neuroendocrine hormone gene expression in the anterior hypothalamus. Mol Endocrinol. 18, :1251-62. Fan, CM, Buttitta L, Mo R, Hui CC. (2003). Interplays of Gli2 and Gli3 and their requirement in mediating Shh-dependent sclerotome induction. Development. 130, :6233-43. Fan CM, Liu C, Goshu E, Wells A.(2003). Identification of the downstream targets of SIM1 and ARNT2, a pair of transcription factors essential for neuroendocrine cell differentiation. J Biol Chem. 278(45):44857-67. Fan CM, Marques G.(2002). Growth arrest specific gene 1: a fuel for driving growth in the cerebellum. Cerebellum. (4):259-63. Fan CM, Buttitta L, Tanaka TS, Chen AE, Ko MS. (2003). Microarray analysis of somitogenesis reveals novel targets of different WNT signaling pathways in the somitic mesoderm. Dev Biol. 258(1):91-104. Fan CM, Liu Y, Liu C, Yamada Y. (2002). Growth arrest specific gene 1 acts as a region-specific mediator of the Fgf10/Fgf8 regulatory loop in the limb. Development. 129(22):5289-300. Fan CM, Goshu E, Jin H, Fasnacht R, Sepenski M, Michaud JL.(2002). Sim2 mutants have developmental defects not overlapping with those of Sim1 mutants. Mol Cell Biol. 22(12):4147-57.

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