Faculty

My lab studies the molecular mechanisms of muscle formation in Drosophila (fruit flies). The key genes and processes involved in muscle formation are conserved between vertebrates and Drosophila. Therefore, the insights we gain using the relatively simple and tractable fly should apply to humans and could lead to breakthroughs in treating and/or preventing muscle-related diseases.

One unusual aspect of fly and human muscles is that each mature muscle is formed from the fusion of several individual muscle precursor cells (myoblasts). Studies from our own and others¹ labs have shown that there are two subclasses of muscle precursors: founders and fusion competent cells. Founders possess all of the information needed to specify the identity of the individual muscles. To "grow", founders fuse to unspecified and undifferentiated "fusion competent cells" until they achieve their mature size.

We have identified a gene, called kirre, that is required for the two subclasses of muscle precursors to recognize and fuse to one another. The kirre protein is expressed specifically on the surface of founders where it interacts with unknown receptors on the surface of fusion competent cells to induce them to migrate toward the founders. kirre also appears to transmit signals that align the membranes of the two cell types and/or mobilize the "fusion machinery". We are now in position to answer two key questions in muscle formation. How do interactions between kirre and its receptor lead to cell fusion? And what other proteins/genes are involved in this process?

To address these questions we are using modern molecular-genetic techniques to identify and characterize the proteins that interact with kirre in the fusion process. Any number of different types of proteins could be involved, e.g., cell surface proteins, components of intracellular signaling pathways, regulators of the cytoskeleton, etc. Their identification will provide insights into the molecular mechanisms by which myoblasts fuse and lead to a more complete understanding of muscle formation.

Representative Publications

• Corbin, V., and T. Maniatis. 1989. The role of transcription interference in the Drosophila melanogaster Adh promoter switch. Nature 337: 279–282.
• Corbin, V., and MT. Maniatis. 1989. The role of specific enhancer-promoter interactions in the Adh promoter switch of D. melanogaster. Genes Dev. 3: 2191–2200.
• Corbin, V., and T. Maniatis. 1990. Identification of cis-regulatory elements required for larval expression of the Drosophila melanogaster alcohol dehydrogenase gene. Genetics 124: 637–646.
• Corbin, V., A.M. Michelson, S.A. Abmayr, V. Neel, E. Alcamo, T. Maniatis, and M.W. Young. 1991. A role for the Drosophila neurogenic genes in mesoderm differentiation. Cell 67:311–323.
• Abmayr, S.M., A.M. Michelson, V. Corbin, M.W. Young, and T. Maniatis. 1991. nautilus, a Drosophila member of the myogenic regulatory gene family. in "Gene Expression in Neuromuscular Development". R. Harwood, ed. Raven Press, USA.
• Lieber, T., S. Kidd, E. Alcamo, V. Corbin, and M.W. Young. 1993. Antineurogenic phenotypes induced by truncated Notch proteins indicate a role in signal transduction, and may point to a novel function for Notch in nuclei. Genes and Dev. 7:1949–1965.
• Burris, P., Zhang, Y., Rusconi, J., and Corbin, V. 1998. The Cytoplasmic and Pore-forming Domains of the Neurogenic Gene Product, BIG BRAIN, are Conserved Between D. virilis and D. melanogaster. Gene 206, 69–76.
• Rusconi, J.C. and Corbin, V. 1998. Evidence for a Novel Notch Pathway Required for Muscle Precursor Selection in Drosophila. Mech. of Development 79, 39–50.
• Rusconi, J.C. and Corbin, V. 1999. A widespread and early requirement for a novel Notch function during Drosophila embryogenesis. Dev. Biol. 215, 388–398.
• Corbin, V., Rusconi, J.C., Bajaj, G.K., Gordon, S.P., Aracena, J.M., Weroha, S.J. Identification and Expression of kirre: a Gene Required for Muscle Fusion. In preparation.

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