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主要是 未知。我们已经发现Lef1介导的Wnt信号在调节中扮演着进化上保守的角色 在焦虑和斑马鱼下丘脑后部抗焦虑神经元的分化中。然而， Lef1靶点、神经发生和行为中神经元功能之间的机制联系尚未得到证实 已经成立了。我们还知道，新的神经元不断地添加到这个脑区，但目前还不清楚 它们会导致与焦虑相关的行为。这一提议将检验Lef1介导的靶基因的假设 调节下丘脑神经发生，以控制一生中与焦虑相关的行为。三个具体目标将 确定哪些Lef1靶点是形成抗焦虑神经元所必需的，这些神经元是否调节 通过HPI轴的应激激素水平，以及胚胎后Lef1依赖的神经发生是否可以 调停行为。这项工作将共同定义一种调节先天行为的新机制 通过神经发生。

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.