ROLE OF CADHERINS IN LAMINAR SYNAPTIC SPECIFICITY

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Synaptic patterning in several regions of the CNS depends on laminar specificity, in which afferent populations confine their synapses to defined subsets of layers, or laminae, within their target region. Studies have implicated the cadherin family of cell adhesion molecules as regulators of selective synaptogenesis. This proposal will test the hypothesis that cadherins are critical for the establishment of lamina-specific connectivity. Experiments will employ the chick optic tectum as a model system, because of its experimental accessibility and well-defined patterns of laminar afferent projections. The first aim is to examine the expression of cadherins in specific tectal laminae, and in their afferent populations, to provide support for a "cadherin code" guiding laminar connectivity. The second aim is to test the role of cadherins in the establishment of laminar-specific connectivity by using gene transfer to achieve loss- or gain-of-function in the tectum in vivo. The third aim is to more precisely examine the role of cadherins in the regulation of retinotectal synapse formation and maturation by using similar gene transfer strategies in vitro. The final aim is to extend these analyses to the protocadherins, a large family of related adhesion molecules about whose function little is known. Together, these studies will advance our understanding of how molecular cues guide the establishment of specific synaptic connections, a process that is critical for the development and normal function of the brain.