Signaling Pathways That Differentiate Dendrite and Axon Development

University Of Michigan At Ann Arbor, Ann Arbor MI

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Abstract

Information processing in the nervous system relies on the separation of dendrites and axons. However, little is known about how dendrites and axons develop into distinct compartments. The long-term goal of this application is to define how neuronal compartmentalization is achieved during the development of neural circuits and how defects in that process lead to neurological and psychiatric diseases. The objective of this application is to delineate the signaling pathways that separate dendrite and axon development. Recent genetic studies have suggested that the fibroblast growth factor (FGF) receptors differentially control dendrite and axon development. The central hypothesis of this application is that the FGF receptors activate distinct signaling pathways to differentially control dendrite and axon development. We will test this hypothesis by pursuing three specific aims: 1) Identify the signaling pathway through which FGF receptors control dendrite-specific development;2) Determine whether FGF receptors regulate axon development through pathways different from dendrite development;3) Identify the effector molecules that execute the dendrite- specific development mediated by Dar1. The approach is innovative because it takes advantage of genetic and novel molecular analyses to investigate the developmental differences between dendrites and axons in vivo. The proposed research is significant because it is expected to advance knowledge of the signaling mechanisms underlying the differential development of dendrites and axons. That knowledge is needed to develop strategies that will allow preferential or specific manipulations of dendrite or axon development in disease conditions and in animal models to interrogate the functions of the nervous system.