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

发育中大脑同源盒 1 (Dbx1) 在先天边缘系统发育中的作用

基本信息

批准号：
8718845
负责人：
Katie Sokolowski
金额：
$ 5.96万
依托单位：
CHILDREN'S RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-07 至 2017-04-06
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8718845
关键词：
Addictive Behavior Adult Amygdaloid structure Anxiety Anxiety Disorders Apoptosis Area Behavior Behavior Control Behavioral Behavioral Genetics Biology Body Weight Brain Brain Diseases Candidate Disease Gene Cells Data Defect Development Developmental Gene Disease Eating Disorders Embryo Event Feeding behaviors Fright Gene Expression Genes Genetic Genetic Programming Hippocampus (Brain)Homeobox Hormone replacement therapy Human Hypothalamic dysfunction Hypothalamic structure Instinct Investigation Knock-out Limbic System Link Mus Mutant Strains Mice Neurodevelopmental Disorder Neurons Neuropeptides Pattern Phenotype Process Prosencephalon Publishing Research Personnel Research Training Role Satiation Shapes Stimulus Stress Structure Systems Development Telencephalon Testing Training Transgenic Mice Work addiction base biological adaptation to stress experience feeding gene function insight interest loss of function mature animal multidisciplinary postnatal progenitor public health relevance response selective expression social stress transcription factor

项目摘要

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.

描述（由申请人提供）：本申请重点研究先天边缘系统行为的发展，特别强调下丘脑。下丘脑接收来自边缘系统结构（包括杏仁核）的主要输入，并在先天厌恶和动机行为（例如压力和进食）中发挥作用。我们之前的研究已经确定了发育中的端脑中不同的祖细胞库（Dbx1+细胞），这些祖细胞库有助于下丘脑分区中出生后神经元细胞的多样性。下丘脑中 Dbx1 基因的缺失导致胚胎和成年动物的基因表达发生变化，这可能解释了这些条件性基因敲除的进食和应激表型。基于这项工作，该项目将测试两个假设。首先，它将检验 Dbx1 是出生后下丘脑神经元发育所必需的假设。其次，它将检验 Dbx1 是下丘脑依赖性先天行为（例如进食和压力）所必需的假设。这些假设的测试将利用条件性功能丧失转基因小鼠的遗传精度来完成。