WILLIAM M. GELBART
Mail: BL 4059
The Biological Labs
16 Divinity Ave
Cambridge, MA 02138
Members of the Gelbart Lab
List of Publications from PubMed
Term: Fall Term And Spring Term 2014-2015.
Instructor: William Gelbart
Course Level: Exclusively for Graduates
Work in our laboratory is aimed at understanding the molecular basis of pattern formation in higher animals. In other words, how does an organism go from a single cell (the newly fertilized egg) to a complex multicellular structure with an enormous diversity of cell types, with each cell deployed in the proper spatial position for its particular physiological role? Further, how does the developmental program that exists in the egg lead to the reliable production of specific pattern elements, such as hands with a very specific set of five fingers in humans?
One important aspect of patterning is the ability of cells within a given tissue primordium to communicate their geographic position and their developmental state to neighboring cells. Our particular focus is on studying an important pathway for such cell-cell signaling using the fruit fly (Drosophila melanogaster) because of the powerful combination of genetic, developmental and molecular tools available in this system.
This signaling system involves the protein product of the decapentaplegic (dpp) gene which we discovered about 15 years ago. The dpp protein is a member of the TGF-ß family of signaling molecules and some family members make fundamental contributions to early vertebrate development as well. The dpp protein is secreted and binds to cell surface receptors on target cells. The dpp signal is necessary for determination of the dorsal ectoderm in the early embryo, for morphogenesis of the gut, for growth in the proximal to distal axis of the adult appendages, for proper oogenesis and patterning of the eggshell, and numerous other developmental events.
Our current focus is on elucidating the cellular and developmental pathways by which the dpp signal acts. We are using a combination of genetic analyses and molecular approaches to address these topics, in particular, focusing on the identification and characterization of genes that encode products which interact with the dpp protein. (1) At the cellular level, we wish to understand the nature of the signal transduction cascade that is activated in cells in which the dpp receptor protein is activated. We now know that dpp receptors are complexes of transmembrane proteins that have extracellular domains that bind dpp protein and intracellular domains that act as serine-threonine protein kinases. Presumably, these kinases act to phosphorylate target proteins in the cell and trigger several sequential signaling steps until finally, the activities of transcription factors in the nuclei of these cells are altered. However, the identities of the proteins involved in this process are known. (2) At the developmental level, we want to understand the role that dpp contributes to pattern formation and how this role is coordinated with other aspects of these pattern formation events. In these processes, we are particularly interested in the processes underlying appendage development, dorsal-ventral patterning of the embryo and eggshell development during oogenesis.
Research topics in the laboratory are numerous, and can range from genetic to embryological to molecular studies or a mix of several of these approaches.
Raftery, L.A., T. Twombly, K. Wharton and W.M. Gelbart, 1995. Genetic screens to identify elements of the decapentaplegic signaling pathway in Drosophila. Genetics 139: 241p;254.
Sanicola, M., J. Sekelsky, S. Elson and W.M. Gelbart, 1995. Drawing a stripe in Drosophila imaginal disks: Negative regulation of decapentaplegic and patched expression by engrailed. Genetics 139: 745p;756.
Sekelsky, J.J., S.J. Newfeld, L.A. Raftery, E.H. Chartoff and W.M. Gelbart, 1995. Genetic characterization and cloning of Mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster. Genetics 139: 1347p;1358.
Letsou, A., K. Arora, J.L. Wrana, K. Simin, V. Twombly, J. Jamal, K. Staehlingp;Hampton, F.M. Hoffmann, W.M. Gelbart, J. Massague and M.B. O'Connor, 1995. Drosophila Dpp signaling is mediated by the punt gene product: a dual ligandp;binding type II receptor of the TGFp; receptor family. Cell 80: 899p;908.
Newfeld, S.J. and W.M. Gelbart, 1995. Identification of two Drosophila TGFp; family members in the grasshopper Schistocerca americana. J. Mol. Evol. 41: 155p;160.
Wharton, K., R.P. Ray, S.D. Findley, H.E. Duncan and W.M. Gelbart, 1996. Molecular lesions associated with alleles of decapentaplegic identify residues necessary for TGFp; BMP cell signaling in Drosophila melanogaster. Genetics 142: 493p;505.
Krueger, N.X., D. Van Vactor, H.I. Wan, W.M. Gelbart, C.S. Goodman and H. Saito, 1996. The transmembrane tyrosine phosphatase DLAR controls motor axon guidance in Drosophila. Cell 84: 611p;622.
Twombly, V., R.K. Blackman, J. Jin, J.M. Graff, R.W. Padgett and W.M. Gelbart, 1996. The TGFp; signaling pathway is essential for Drosophila oogenesis. Development 122: 1555p;1565.
Newfeld, S.J., E.H. Chartoff, J.M. Graff, D.A. Melton and W.M. Gelbart, 1996. Mothers against dpp encodes a conserved cytoplasmic protein required in DPP/TGFp; responsive cells. Development 122 (in press).
Singer, M.A., A. Penton, V. Twombly, F.M. Hoffmann, and W.M. Gelbart, 1996. Signaling through both type I DPP receptors is required for anteriorp;posterior patterning of the entire Drosophila wing. Development (submitted).