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Senior Scientist, Neuroscience, Ottawa Hospital Research Institute
Department of Cellular and Molecular Medicine, University of Ottawa
Dr. Colavita completed a Ph.D. at the University of Toronto with Joseph Culotti studying the Netrin axon guidance pathway. He then pursued postdoctoral research at Stanford University with Marc Tessier-Lavigne to study molecular mechanisms involved in axon branching.
Human behaviour depends on the coordinated development of billions of neurons into functional circuits and networks. This complexity is attained by the intrinsic properties and shapes of neurons and their remarkable ability to find and make successful connections with each other and their target cells. Our lab uses genetic and molecular approaches in the nematode C. elegans (Fig. 1)to study neuronal migration, axon guidance, and the underlying mechanisms that allow neurons to acquire and maintain characteristics such as polarized cell shapes and branched morphologies that distinguish them from other cell types. Understanding these processes may ultimately lead to the development of new drug targets or therapies that promote neuronal repair following brain injury or neurodegenerative disease.
C. elegans: a powerful model organism for neurobiology research. C. elegans possesses many advantages as a model animal. These include a simple anatomy of 959 somatic cells, rapid generation time (~3 days), a fully sequenced genome, transparent bodies to facilitate in vivo imaging, and a powerful collection of genetic and molecular tools. C. elegans is especially well suited for research in neurobiology given that the axonal wiring and synaptic connectivity of its relatively simple nervous system of 302 neurons is completely described and annotated. While C. elegans is a simple animal, it shares many of the same biological pathways and genetic mechanisms that are found in more complex organisms.
Understanding the role of planar cell polarity (PCP) signaling in nervous system development. Wnt/Frizzled signaling pathways are critically important during development with roles in cell and tissue identity, organization, and morphogenesis. One such pathway, known as the planar cell polarity (PCP) pathway is a key regulator of cell polarity and alignment in the plane of epithelial tissues. In addition to Wnts and Frizzleds, genetic studies in flies and mammals havedefined a core group of conserved PCP molecules that include Van Gogh and Prickle (known as VANG-1 and PRKL-1 in C. elegans). Our lab has recently found that a PCP-related pathway is involved in restricting neurite emergence or extension in VC neurons to specific trajectories in C. elegans. The VC neurons (VC1-6) are an ideal axon guidance and neuronal polarity model as they display stereotypical differences in axon extension along the anterior-posterior (AP) body axis. VC1-3 and VC6 project processes bidirectionally along the AP axis, whereas VC4 and VC5 project processes along an orthogonal axis generated during organogenesis. In vang-1 and prkl-1 mutants, the normally bipolar VC4 and VC5 neurons undergo a gradual loss of polarity that results in inappropriate neurite extension along the AP axis (Fig. 2). Defining the PCP-like mechanism that inhibits neurite formation is currently a major focus of the lab.
planar cell polarity, axon guidance, axon regeneration, C.elegans