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In the developing nervous system, an enormous number and diversity of neurons are precisely organized into neural circuits. How can such a vast set of neural connections be wired using limited cues encoded in our genomes? To tackle this problem, we are studying a family of neuronal receptors with an extraordinary potential for conferring cell-surface diversity and wiring specificity. The clustered Protocadherin genes (Pcdhs) are tandemly arrayed on a single genomic locus and encode ~60 cadherin-related transmembrane proteins that are combinatorially expressed among single neurons. We propose that the Pcdhs serve as a code for ‘neuron individuality’ to mediate complex patterns of connectivity. I will discuss our recent work on the roles of Pcdhs in regulating the survival and integration of GABAergic inhibitory interneurons during circuit development throughout the brain. These studies will yield new insights on the cell-cell interactions and molecular cues that establish the proper balance and wiring of inhibitory cells into circuits. I will also present work on cellular mechanisms that shape the morphologies of interneurons.

The MacIntosh Lectureship supports special seminars in honor of Dr. F.C. MacIntosh.