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David Van Vactor,Ph.D.

Professor of Cell Biology

Harvard Medical School
Cell Biology, LHRRB - 409
45 Shattuck St
Boston, MA 02115
Telephone: 617-432-2195
Fax: 617- 432-2808
E-mail: davie@hms.harvard.edu
Predocs: 2 Postdocs: 6 Completed PhD's: 4

  

The mechanisms that guide neuronal processes to their ultimate sites of synaptic contact are crucial for establishing the complex, functional architecture of the nervous system. The problem of understanding these mechanisms is one of the oldest and most challenging issues in developmental neurobiology. Examples from many organisms have demonstrated the requirement of specific cellular interactions for the correct axon pathfinding or connectivity of particular neurons, suggesting the existence of guidance cues that direct individual axons to their targets. Our lab is interested in finding the key molecules that control axon guidance and target recognition. Ultimately we want to know how these molecules act in concert to determine the directional specificity of axonal outgrowth.

The embryonic pattern of neuromuscular connectivity in Drosophila is an excellent system for the study of axon guidance and synaptic specificity at a molecular level. Normal neuromuscular development has been characterized in this model system at a single cell resolution, both presynaptically and postsynaptically, from the onset of axonogenesis through the physiological maturation of neuromuscular junctions. Using both classical and molecular genetics, we have begun to dissect the mechanisms that control the navigational choices of particular motor axons and the morphogenesis of their synaptic contacts with specific target muscles. For example, one group of axons requires the function of a receptor-like protein tyrosine phosphatase (Dlar) to enter the appropriate target region. Our ongoing studies of the Dlar pathway, which appears highly conserved from fly to man, suggest that signaling pathways converge downstream of the receptor to control cytoskeletal assembly.

 

References:

  • Wills, Z., Marr, L., Zinn, K., Goodman, C.S. and Van Vactor, D. (1999) Profilin and the Abl Tyrosine Kinase are Required for Motor Axon Outgrowth in the Drosophila Embryo. Neuron 22, 291-299.
  • Wills, Z., Bateman, J., Korey, C., Comer, A., and Van Vactor, D. (1999) The Tyrosine Kinase Abl and its Substrate Enabled Collaborate with the Receptor Phosphatase Dlar to Control Motor Axon Guidance. Neuron 22, 301-312.
  • Bateman, J., Shu, H., Van Vactor, D. (2000) The Guanine Nucleotide Exchange Factor Trio Mediates Axonal Development in the Drosophila Embryo. Neuron 26, 93-106.
  • Bateman, J., Reddy, R.S., Saito, H. and Van Vactor, D. (2001) The receptor tyrosine phosphatase Dlar and integrins organize actin filaments in the Drosophila follicular epithelium. Current Biology, 11:1317-1327.
  • Kaufmann, N., DeProto, J., Ranjan, R., Wan, H. and Van Vactor, D. (2002) Drosophila Liprin-a and the Receptor Phosphatase Dlar Cooperate During Synapse Morphogenesis. Neuron, 34, 27-38.