Genetic analysis of nematode cell differentiation

描述(申请人提供)：我们将继续研究线虫线虫神经元分化和功能所需的基因。大部分研究将像过去一样，集中在分析六个触摸感受器神经元(TRN)的发育和活动上。在这项资助下之前的研究已经确定了TRN的生成、规范、维护和功能所需的基因。特别是，在上一次资助期间，我们将TRN表达基因的集合扩大了8倍，达到约200个基因，确定了将TRN发育限制在6个细胞中的成分，并确定了在这些细胞中感觉接触的转导复合体。最后一个复合体是在真核生物机械感觉神经元中发现的第一个转导复合体。我们还开发了几种新方法，我们将在即将到来的资金期利用这些方法。特别是，我们将研究细胞命运是如何决定和维持的，以及脂双层和细胞外基质如何影响机械感觉。该建议的具体目的是：1)研究有丝分裂后基因表达的调控，特别是研究神经元发育早期所需的基因是如何被关闭的；2)研究TRNS内细胞类型指定的基础；3)表征MEC-4通道复合体和类似蛋白质的脂结合和调节成分；以及4)研究细胞外基质(ECM)在触摸敏感性中的作用。拟议中的实验的第二个结果将是发现线虫神经系统一般发育和功能所需的丰富基因。 公共卫生相关性：我们研究了线虫中神经细胞发育和触觉细胞功能的遗传控制。我们研究的许多基因在人类中都有对应的基因(其中一些是遗传病的基础)，但我们可以在这个有机体中更好地研究它们的功能。通过识别神经生长和机械敏感性所需的分子，我们获得了对人类生物学和健康的一般理解有用的基本知识，例如，研究人员使用我们的分子模型来指导他们的研究，研究血压传感。

DESCRIPTION (provided by applicant): We will continue our study of genes needed for neuronal differentiation and function in the nematode Caenorhabditis elegans. Most of the research will center, as in the past, on the analysis of the development and activity of the six touch receptor neurons (TRNs). Previous research under this grant has identified genes needed for the generation, specification, maintenance and function of the TRNs. In particular in the last funding period we enlarged the collection of TRN-expressed genes 8-fold to approximately 200 genes, identified components that restrict TRN development to six cells, and identified the transduction complex that sense touch in these cells. This last complex is the first transduction complex to be identified in any eukaryotic mechanosensory neuron. We also developed several new methods that we will exploit in the upcoming funding period. In particular we will investigate how cell fate is determined and maintained and how the lipid bilayer and extracellular matrix affect mechanosensation. The specific aims of the proposal are: 1) to investigate the regulation of post-mitotic gene expression, particular examining how genes needed only early in development of neurons are turned off; 2) to investigate the basis of cell-type specification within the TRNs; 3) to characterize lipid- binding and modulating components of the MEC-4 channel complex and similar proteins; and 4) to investigate the role of the extracellular matrix (ECM) in touch sensitivity. A secondary consequence of the proposed experiments will be the discovery a wealth of genes needed for general development and function of the C. elegans nervous system. PUBLIC HEALTH RELEVANCE: We study the genetic control of nerve cell development and function of touch sensory cells in the nematode Caenorhabditis elegans. Many of the genes we study have counterparts in humans (some being the basis of inherited diseases), but we can study their function much better in this organism. By identifying molecules needed for nerve growth and mechanosensitivity, we gain basic knowledge that is useful in the general understanding of human biology and health, as evident, e.g., by researchers studying the sensing of blood pressure using our molecular models to guide their research.