Genetic Regulation of Telencephalon Development

University Of California, San Francisco, San Francisco CA

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Abstract

DESCRIPTION (provided by applicant): There are two general types of telencephalic GABAergic neurons: projection neurons of the basal ganglia and local circuit neurons of cortical structures (olfactory bulb, cerebral cortex, hippocampus, pallial amygdala). Most GABAergic neurons in the adult brain are inhibitory;their dysfunction leads to severe disorders including epilepsy and Huntington's disease, and abnormalities in their functions are implicated in a range of neuropsychiatric disorders including schizophrenia and autism. Inroads to understanding the genetic control of GABAergic neuron development and function have begun. In the forebrain, the Dlx1, 2, 5 &6 homeobox genes have a central role in this process. We hypothesize that pairs of these transcription factor-encoding genes are required for regulating early steps in GABAergic neuronal differentiation, whereas individual Dlx genes are required for later steps in differentiation and neural function. Herein, I describe experiments using gene expression assays and mouse mutants that are aimed at elucidating some of the molecular mechanisms through which the Dlx genes regulate development and function of telencephalic GABAergic neurons.