Mechanism and function of Lef1-mediated hypothalamic neurogenesis.

在不同物种之间建立先天行为的遗传和分子机制在很大程度上

The genetic and molecular mechanisms that establish innate behaviors across diverse species are largely unknown. We have discovered an evolutionarily conserved role for Lef1-mediated Wnt signaling in the regulation of anxiety and in the differentiation of anxiolytic neurons in the zebrafish posterior hypothalamus. However mechanistic links between Lef1 targets, neurogenesis, and neuronal function in behavior have not yet been established. We also know that new neurons are continually added to this brain region, but it is not clear whether they contribute to anxiety-related behavior. This proposal will test the hypothesis that Lef1-mediated target genes regulate hypothalamic neurogenesis to control anxiety-related behavior throughout life. Three specific aims will determine which Lef1 targets are required for the formation of anxiolytic neurons, whether those neurons regulate stress hormone levels through the HPI axis, and whether postembryonic Lef1-dependent neurogenesis can mediate behavior. Together this work will define a novel mechanism for the regulation of an innate behavior through neurogenesis.