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Genetic and Hormonal Mechanisms of Sex Differences in the Nervous System

神经系统性别差异的遗传和激素机制

基本信息

批准号：
8611058
负责人：
Douglas S Portman
金额：
$ 26.59万
依托单位：
UNIVERSITY OF ROCHESTER
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：
2014-09-01 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8611058
关键词：
Adult Afferent Neurons Animal Model Animals Behavior Biological Biological Models Brain Caenorhabditis elegans Cells Chemoreceptors Collaborations Complex Cues Data Development Disease Food Future Gene Expression Genetic Genetic Models Goals Gonadal Steroid Hormones Hormonal Hormones Individual Invertebrates Ligands Link Modeling Molecular Molecular Genetics Mus Nematoda Nervous system structure Neurologic Neurons Neurophysiology - biologic function Odors Outcomes Research Partner in relationship Pathway interactions Property Psychopathology Research Resolution Role Sensory Sex Bias Sex Characteristics Sex Chromosomes Signal Transduction Specific qualifier value Steroids System Time Work base brain behavior functional genomics genetic effector nervous system disorder neurodevelopment neurophysiology neuropsychiatry neuroregulation novel programs relating to nervous system sex sex determination stem steroid hormone transcription factor

项目摘要

! Though they have important significance for many neuropsychiatric and neurological disorders, sex differences in the brain and the mechanisms that underlie these remain poorly understood. Importantly, recent studies have highlighted the key role of genetic sex in the nervous system, which acts together with hormonal cues to regulate sexual differentiation of the brain and of behavior. However, very little is known about how genetic sex might modulate neural development and function. Here, we take advantage of a recently described sex difference in the function of a single C. elegans sensory neuron pair, AWA, to better understand these pathways. Because there is strong evidence that conserved mechanisms that link genetic sex to neural function, these studies will provide a mechanistic framework that will enable future candidate-driven studies in mammalian systems. Based on extensive preliminary data, we hypothesize that cell-autonomous “genetic sex” dynamically modulates TGFβ signaling to bring about the sex difference in AWA sensory function. In Aim 1, we will identify transcription factors that specify the sexually dimorphic state of the AWA neurons using two complementary functional genomic approaches. In Aim 2, we will identify the regulatory mechanism targeted by genetic sex to modulate AWA function. Recent data indicate that TGFβ signaling is likely to be this mechanism. In Aim 3, we will identify the mechanism that controls the timing of the effects of genetic sex on AWA. Steroid hormone signaling has been implicated in this role, indicating that there may be deep evolutionary connections between steroids and genetic sex. Together, these studies will provide an integrated molecular-genetic framework that links genetic sex to a terminal effector of behavior, something that currently exists in no system. ! ! ! !

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