Genetic control of sex differences in the nervous system

摘要 神经系统和行为的性别差异在动物中是普遍存在的 王国除了它们的基本生物学兴趣之外，这些差异还具有重要的 理解性别偏见的含义，许多心理健康的特点， 神经系统疾病一个有趣的，但知之甚少的组成部分， 系统的性别差异是通过非依赖性的、细胞内在的 “神经性”在神经系统的塑造特征。在初步工作中， 线虫C.我们已经确定了嗅觉行为的强烈性别差异， 这种变化是通过细胞内在的、依赖于性别的神经元功能改变而产生的 两性都有了解这些性行为背后的机制 差异有很大的潜力，阐明类似的现象，在 哺乳动物中枢神经系统在三个具体目标中，我们将（1）确定精确的神经病灶， 调节嗅觉中的性别差异，并描述嗅觉中的性别差异。 这些神经元的发育和功能;（2）也使用候选基因方法 作为靶向微阵列研究，以确定核心神经系统中的性别调控基因， 系统，并确定其功能意义;（3）描述C. 线虫属保守的DM家族性调节因子的成员，包括dmd-3， 从而产生嗅觉的性别差异。总之，这项工作采取了创新的方法， 阐明保守的分子，遗传和神经机制， 性别与神经系统发育和功能的性别差异有关。敷设总结 利用一个微小的土壤蛔虫，我们将研究性别的遗传和细胞调节 神经系统发育和功能的差异。这些研究将 确定可能在人类心理健康中发挥重要作用的基因和机制 和神经系统疾病，如自闭症，情绪障碍和慢性疼痛 综合征，这优先影响一个性别超过其他。

Abstract Sex differences in the nervous system and in behavior are ubiquitous in the animal kingdom. Beyond their basic biological interest, these differences have important implications for understanding the sex bias that characterizes many mental health and neurological disorders. An intriguing but poorly understood component of nervous system sex differences arises through the actions of hormone-independent, cell-intrinsic "neural sex" in shaping characteristics of the nervous system. In preliminary work using the nematode C. elegans, we have identified robust sex differences in olfactory behavior that arise through cell-intrinsic, sex-dependent modification of the function of neurons common to both sexes. Understanding the mechanisms that underlie these sex differences has great potential to shed light on similar phenomena acting in the mammalian CNS. In three Specific Aims, we will (1) identify the precise neural foci that regulate sex differences in olfaction, and characterize sex differences in the development and function of these neurons; (2) use a candidate-gene approach as well as targeted microarray studies to identify sex-regulated genes in the core nervous system and determine their functional significance; and (3) characterize the role of C. elegans members of the conserved DM family of sexual regulators, including dmd-3, in generating sex differences in olfaction. Together, this work takes an innovative approach to illuminating the conserved molecular, genetic and neural mechanisms by which neural sex is coupled to sex differences in the development and function of the nervous system. Lay summary Using a tiny soil roundworm, we will examine the genetic and cellular regulation of sex differences in the development and function of the nervous system. These studies will identify genes and mechanisms that may have important roles in human mental health and neurological conditions, such as autism, mood disorders and chronic pain syndrome, that preferentially affect one sex over the other.