The role of Developing Brain Homeobox 1 (Dbx1) in innate limbic system developmen

描述（由申请人提供）：本申请主要研究先天边缘系统行为的发展，特别强调下丘脑。下丘脑接受包括杏仁核在内的边缘系统结构的主要输入，并在天生的厌恶和动机行为（如压力和进食）中发挥作用。我们之前的研究已经在发育中的端脑中发现了不同的祖细胞池（Dbx1+细胞），它们有助于下丘脑细分的出生后神经元细胞多样性。下丘脑中Dbx1基因的缺失导致胚胎和成年动物基因表达的变化，这可能解释了这些条件敲除的摄食和应激表型。在此基础上，本项目将检验两个假设。首先，它将测试Dbx1是出生后下丘脑神经元发育所必需的假设。其次，它将测试Dbx1是下丘脑依赖性先天行为（如进食和压力）所必需的假设。测试这些假设将完成使用基因精度的条件功能丧失转基因小鼠。

DESCRIPTION (provided by applicant): This application is focused on the study of the development of the innate limbic system behaviors, with a particular emphasis on the hypothalamus. The hypothalamus receives major inputs from limbic system structures, including the amygdala, and functions in innate aversive and motivational behaviors such as stress and feeding. Our previous studies have identified distinct progenitor pools (Dbx1+ cells) in the developing telencephalon that contribute to postnatal neuronal cell diversity in hypothalamic subdivisions. Deletion of the Dbx1 gene in the hypothalamus caused changes in gene expression in embryonic and adult animals, potentially explaining the feeding and stress phenotype of these conditional knockouts. Based on this work, this project will test two hypotheses. First, it will test the hypothesis that Dbx1 is required for the development of postnatal hypothalamus neurons. Second, it will test the hypothesis that Dbx1 is required for hypothalamic-dependent innate behaviors such as feeding and stress. Testing of these hypotheses will be accomplished using the genetic precision of conditional loss of function transgenic mice.