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Cell fate specification in the central nervous system

The nervous system consists of a great variety of neurons and glia that together form the components and circuits necessary for nervous system function. Neuronal and glial diversity are generated through a series of highly orchestrated events that control cell numbers, subtype identity, cell morphology and axonal projection patterns. Defining how these events unfold and integrate at the molecular level during development will provide significant insight into the basic mechanisms involved in establishing the mature nervous system, and importantly provide an understanding of the links between development, disease and therapeutic strategies.

My laboratory uses the developing spinal cord as our major paradigm to define the mechanisms that maintain an undifferentiated progenitor state and the molecular pathways that trigger their differentiation into postmitotic, terminally differentiated neurons and glia. Our experimental systems are the mouse and chick, and we utilize an integrated approach that includes molecular biology, biochemistry, developmental biology, genetics and behavior. Current projects include the functional analysis of a new family of six transmembrane proteins and the regulatory roles of thiol-redox cascades in nervous system development. We are particularly interested in how these control systems integrate with known signaling pathways to regulate the onset and progression of neuronal and glial differentiation. In related projects, we hope to explore if developmental dysfunction contributes to neurodegeneration, and if developmental mechanisms can be exploited to increase axonal regeneration and repair.