[ Research Interests ] [ Representative Publications ]

Mark Van Doren Associate Professor Department of Biology Co-Director, CMDB Graduate Program B.A. Cornell University Ph.D. University of California, San Diego Postdoctoral Whitehead Institute (MIT) and Skirball Institute (NYU Medical Center)

Department of Biology Johns Hopkins University 3400 North Charles Street Baltimore, MD 21218-2685 U.S.A. Office Telephone: Lab Telephone: Department Fax: Email: 410.516.4717 410.516.4830 410.516.5213 vandoren@jhu.edu  Office- Mudd 305B   Lab- Mudd 302

Research Interests Research in our laboratory focuses on the early development of the primordial germ cells and gonad. Germ cells are the only cells that contribute to the next generation of a species, and so an organism's primary goal is to ensure that these cells are successful. The interactions that germ cells have with somatic cells within the gonad are critical for their proper development. Germ cells play an important role in human health, and improper germ cell development can lead to infertility or the formation of germ cell cancers. Despite the importance of the germ cells, little is understood about the molecular mechanisms controlling their development. We have chosen to study germ cell development in Drosophila to take advantage of the many genetic, molecular and cell biological tools available in this system. Many of the same developmental issues are faced by germ cells in a wide variety of species, and different organisms are likely to solve these problems in similar ways. Once we gain an understanding of the molecular mechanisms controlling germ cell development in Drosophila, we can then apply this knowledge to germ cell development in other species. Our research encompasses three fundamental aspects of early germ cell development: germ cell identity, gonad morphogenesis and gonad sexual dimorphism. Germ Cell Identity How is a cell designated to become a germ cell? What aspects of germ cell identity allow these cells to give rise to a whole new organism? The germ cells in Drosophila obtain their identity through a combination of intrinsic and extrinsic cues. Cells are initially chosen to become germ cells by inheriting a specialized cytoplasm, the germ plasm, during the initial rounds of cell division in the early embryo. Later, they are exposed to a variety of cues from the somatic cells of the gonad that also play a critical role in regulating germ cell identity. We are interested in determining what the molecular nature of these intrinsic and extrinsic factors are and how they induce a cell to express the unique program of germ cell development. Gonad Morphogenesis The germ cells undergo a directed cell migration to reach the proper somatic cells with which they will form the gonad. How do these cells recognize one another and undergo the morphogenetic movements required to form a properly shaped and patterned gonad? This process is essential for continued germ cell development, and is also a model for the cellular interactions and changes in morphology that occur during the formation of all organs. We have identified a novel gene, fear of intimacy, that is essential for gonad morphogenesis. The homophilic cell adhesion molecule E-cadherin is also required, and appears to be regulated by fear of intimacy. We are currently investigating how these factors regulate gonad morphogenesis, and what other molecules and mechanisms are acting in this process. Sexual Dimorphism How is an individual instructed to develop with one of two distinct sexual phenotypes, male or female? The choice between male and female is initiated by a sex determination "switch", a genetic or environmental signal that controls sexual identity. Little is known about how a sex determination switch can lead to sexually dimorphic development. Sexual dimorphism in the gonad is particularly important, since the gonad must generate distinct male or female gametes for reproduction, and often controls the sexual development of other parts of the body. We are studying gonad sexual dimorphism in Drosophila. We have found that the somatic cells of the gonad are already different in males and females at the time of gonad formation, and that these somatic cells direct regulate proper male or female development of the germ cells. Furthermore, genes that are required for proper sex determination in humans also appear to play similar roles in Drosophila. We are currently investigating the molecular mechanisms that control gonad sexual dimorphism, and determining whether these mechanisms are evolutionarily conserved.   Representative Publications DeFalco, T.J., Camara, N., Le Bras, S. and Van Doren, M. 2008. Non-autonomous sex determination controls sexually dimorphic development of the Drosophila gonad. Developmental Cell. In Press. Van Doren, M. 2007. Much HUBbub about stem-cell niches. Nature Cell Biology. 9: 1344-1245. Casper, A. and Van Doren, M. 2006. The control of sexual identity in the Drosophila germline. Development. 133.2783-2791. Mathews, W.R., Ong, D., Milutinovich, A.J., and Van Doren, M. 2006. Zinc transport activity of Fear of Intimacy is essential for proper gonad morphogenesis and DE-cadherin expression. Development 133:1143-1153. LeBras, S. and Van Doren, M. 2006. Development of the male germline stem cell niche in Drosophila. Developmental Biology. 294:92-103. Wawersik, M., Milutinovich, A.B., Matunis, E., Williams, B. and Van Doren, M. 2005. Somatic control of germline sexual development is mediated by the JAK/STAT pathway. Nature. 436:563-567. Wawersik, M. and Van Doren, M. 2005. nanos is required for formation of the spectrosome, a germ cell-specific organelle. Developmental Dynamics. 234:22-27. DeFalco, T.J., Le Bras, S. and Van Doren. M. 2004. Abdominal-B is essential for proper sexually dimorphic development of the Drosophila gonad. Mechanisms of Development. 121:1323-1333. Mathews, W.R., Wang, F., Eide, D.J. and Van Doren, M. 2005. Drosophila fear of intimacy encodes a Zrt/IRT-like protein (ZIP) family zinc transporter functionally related to mammalian ZIP proteins. J. Biological Chemistry. 280:787-795. DeFalco, T., Verney, G., Jenkins, A., McCaffery, M., Russell, S. and Van Doren, M. 2003. Sex-specific programmed cell death controls sexual dimorphism in the Drosophila embryonic gonad. Developmental Cell. 5:205-16. Jenkins, A., McCaffery, M. and Van Doren, M. 2003. E-cadherin is essential for proper germ cell-soma interaction during gonad morphogenesis. Development. 130: 4417-26. Van Doren, M., Mathews, W., Samuels, M., Broihier, H.T., Moore, L.A., and Lehmann, R. 2003. Fear of Intimacy encodes a conserved cell surface protein required for morphogenesis of the Drosophila gonad. Development.130:2355-2364. These papers have been featured in a Current Biology Dispatch article by D. Godt and U. Tepass. Curr. Biol. 13:R683-5 Van Doren, M., Moore, L.A., Broihier, H.T., and Lehmann, R. 1998. HMG-CoA reductase guides migrating primordial germ cells. Nature. 396:466-469. Van Doren, M., Williamson, A.L. and Lehmann, R. (1998). Regulation of zygotic gene expression in Drosophila primordial germ cells. Current Biology. 8:243-246. Van Doren, M.#, Moore, L.A., Broihier, H.T., Lunsford, L. and Lehmann, R. 1998. Identification of genes controlling germ cell migration and embryonic gonad formation in Drosophila. Development. 125:667-678.

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