A Novel Gene Affecing Neuronal Cell Fate Specification

描述（由申请人提供）：虽然已经发现了细胞命运特化的许多基本原理，但创造如此巨大的神经元多样性的机制仍然没有得到很好的理解。神经分化通常被认为是一个两步过程，一个是建立一般的神经命运，第二个是进一步分化细胞类型。这种特化可以更进一步，因为在双侧生物体中，最初命运相似的右侧和左侧神经元通常获得不同的功能。这项建议将研究这些步骤之间的联系，通过分析一个基因，影响收购的一般和特定的细胞命运的秀丽隐杆线虫ASE味觉神经元的分化。在筛选双侧对称ASE神经元中的侧向不对称缺陷时，一个令人惊讶的突变体不仅影响神经元获得左右命运的能力，而且还影响神经元完全获得ASE命运的能力。这是第一个在这种情况下被从屏幕上拉出来的突变体。在这个提议中，突变体将被表征，映射和克隆，并功能解剖。初步观察表明，该基因可能参与建立ASE细胞命运和促进一些左右细胞命运标志物的不对称表达。

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.