Molecular Controls of Asymmetric Division in C. elegans

描述(由申请人提供)： 细胞不对称分裂是后生动物实现细胞多样性的一般机制，因此对我们对发育和遗传病的长期理解至关重要。线虫的体细胞性腺前体(SGPS)经历不对称的细胞分裂，建立性腺的近-远端轴。由于这种不对称分裂，POP-1/TCF在SGP子代中以不同方式定位。Wnt途径调节POP-1的定位，细胞周期机制的组成部分和TRA-1/GLI转录因子也是如此。然而，这些调控因子控制POP-1不对称性的机制尚不清楚。这项建议的主要目标是以线虫的性腺为模型，了解细胞不对称分裂如何受到调控的分子机制。为此，将确定Wnt途径控制POP-1在SGPS中不对称定位的机制。细胞-细胞接触在调节Wnt途径中的潜在作用将被检验。最后，在线虫中使用正向和反向遗传学方法将识别在不对称分裂中发挥功能的新基因，包括TRA-1/GLI和细胞周期机制的潜在靶点。

DESCRIPTION (provided by applicant): Asymmetric cell division is a general mechanism of achieving cellular diversity in metazoans and therefore vital to our long-term understanding of development and genetic disease. The somatic gonadal precursors (SGPs) of C. elegans undergo asymmetric cell division, establishing the proximal-distal axis of the gonad. As a result of this asymmetric division, POP-1/TCF is differentially localized in the SGP daughters. The Wnt pathway regulates POP-1 localization, as does components of the cell cycle machinery and the TRA-1/GLI transcription factor. However, the mechanism by which these regulators control POP-1 asymmetry is unknown. The broad goal of this proposal is to understand the molecular mechanisms of how asymmetric cell division is regulated, using the gonad of C. elegans as a model. To this end, the mechanism underlying the control of the Wnt pathway on the asymmetric localization of POP-1 in the SGPs will be determined. A potential role of cell-cell contact in regulating the Wnt pathway will be examined. Finally, use of both forward and reverse genetics methods available in C. elegans will identify new genes that function in asymmetric division, including potential targets of TRA-1/GLI and the cell cycle machinery.