A Novel Gene Affecing Neuronal Cell Fate Specification

描述(由申请人提供)：虽然已经发现了一些潜在的细胞命运决定的原则，但创造如此巨大的神经元多样性的机制仍然不太清楚。神经分化通常被认为是一个两步走的过程，一个是确定一般的神经命运，另一个是进一步区分细胞类型。这一规范可以更进一步，因为在双边生物体中，最初命运相似的左右两侧的神经元往往具有不同的功能。这项建议将通过分析影响秀丽线虫味觉神经元获得一般和特定细胞命运的基因来研究这些分化步骤之间的联系。在筛选两侧对称的ASE神经元的侧向不对称缺陷时，一个令人惊讶的突变不仅影响了神经元获得左、右命运的能力，而且还影响了完全获得ASE命运的能力。这是第一个在这种情况下被从屏幕上删除的此类突变。在这项提议中，将对突变体进行表征、映射和克隆，并对其进行功能解剖。初步观察表明，该基因可能参与了ASE细胞命运的建立，并促进了一些左右细胞命运标记的不对称表达。

DESCRIPTION (provided by applicant): While a number of principles underlying cell fate specification have been discovered, the mechanisms that create such vast neuronal diversity are still not well understood. Neural differentiation is often thought of as a two step process, one that establishes general neural fate and a second that further differentiates cell types. This specification can be taken a step further as in bilateral organisms, initially similarly-fated neurons on the right and left sides often acquire different functions. This proposal will study links between these steps of differentiation by analyzing a gene that affects the acquisition of both general and specific cell fates in the Caenorhabditis elegans ASE taste neurons. In a screen for lateral asymmetry defects in the bilaterally symmetric ASE neurons, one surprising mutant affects the neurons' ability to not only acquire left and right fate, but also to acquire ASE fate altogether. It is the first mutant of its kind to be pulled out of a screen in this context. Within this proposal, the mutant will be characterized, mapped and cloned, and functionally dissected. Initial observations suggest that this gene could be involved both in establishing ASE cell fate and in promoting the asymmetric expression of a number of right and left cell fate markers.