Genetic mechanisms that regulate left/right asymmetric neuron size

描述(由申请人提供)： 项目摘要《左/右不对称神经元大小的遗传和功能分析》神经系统通常在结构水平上是两侧对称的，但在功能水平上是高度侧化的(左/右不对称)。与功能偏侧性相关的分子和形态是稀疏的，因此，对功能偏侧性知之甚少。然而，人们已经注意到，在功能偏侧的脑区，对称放置的双侧神经元群的胞体大小不同。决定这些左右不对称胞体大小差异的遗传机制尚不清楚。事实上，人们通常不太清楚神经细胞的胞体大小是如何在整个神经系统(包含大小相差几个数量级的神经元)中被控制的。我们建议利用线虫来研究两个两侧对称的化学感觉神经元的大小差异是如何受到基因控制的。为了识别基因，我们在一大组不同的遗传突变背景中可视化神经元对的大小差异，这影响了以前已知的在其他系统中控制细胞大小的途径。我们将研究这些假定的大小调节因子在哪里表达，以及它们的表达是如何调控的。我们将测试改变两个神经元的大小是否会影响对感觉线索的特定反应参数。总而言之，我们结合了两个令人兴奋和积极追求的研究领域，这两个领域以前从未结合在一起-神经系统左/右不对称的研究和大小控制的研究，使用了一个特别适合研究这些问题的模型系统。 公共卫生相关性： 项目简介“左/右不对称神经元大小的遗传和功能分析”这项拨款提案开始分析神经系统中细胞大小差异的遗传调节和功能相关性，使用线虫作为模型系统。神经细胞大小的横向差异在系统发育过程中是保守的，可以在人类中观察到，并在精神障碍中被破坏，说明了这项研究的总体重要性。

DESCRIPTION (provided by applicant): PROJECT SUMMARY "Genetic and functional analysis of left/right asymmetric neuron size" Nervous systems are generally bilaterally symmetric on a structural level but are strongly lateralized (left/right asymmetric) on a functional level. Molecular and morphological correlates of functional laterality are sparse and, therefore, functional lateralization is poorly understood. However, it has been noted that symmetrically positioned, bilateral groups of neurons in functionally lateralized brain regions differ in the size of their soma. The genetic mechanisms that program these left/right asymmetric soma size differences are unknown. In fact, it is generally not well understood how the soma size of neurons is controlled throughout the nervous system (which contains neurons that differ in size by several orders of magnitude). We propose here to utilize the nematode C.elegans to study how the size difference of two, otherwise bilaterally symmetric chemosensory neuron is genetically controlled. To identify genes, we visualize the size difference in the neuron pair in a large panel of different genetic mutant backgrounds, which affect previously known pathways that control cell size in other systems. We will examine where these presumptive size regulators are expressed and how their expression is regulated. We will test whether altering the size of the two neurons impacts on specific response parameters to sensory cues. In sum, we combine two exciting and actively pursued areas of research that have not been combined before - the study of left/right asymmetry in the nervous system and the study of size control, using a model system that is particularly amenable to study these problems. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE "Genetic and functional analysis of left/right asymmetric neuron size" This grant proposal sets out to begin an analysis of the genetic regulation and functional relevance of cell size differences in the nervous system, using the nematode C.elegans as a model system. Lateral differences in neuron cell size are conserved across phylogeny, can be observed in humans and are disrupted in psychiatric disorders, illustrating the overall importance of this study.