Analysis of mes-1, a C. elegans Gene Involved in Asymmetric Embryonic Divisions

不对称细胞分裂产生具有不同发育命运的子细胞。本研究探讨了母体提供的因子如何控制秀丽隐杆线虫早期胚胎的不对称分裂。母体效应基因mes- 1在促进不平等分裂产生体细胞创始细胞和生殖谱系中起着至关重要的作用。mes-1母亲的后代是不育的，因为原始生殖细胞P4转化为肌肉前体，就像它的体细胞姐妹细胞一样，这种细胞命运转变的潜在原因是产生P4的细胞中纺锤体不对称的丧失和细胞质分配缺陷。Strome博士对突变表型的研究提出了几种MES-1如何参与促进胚胎细胞不平等分裂和不平等分配的模型。MES-1包含一个假定的跨膜结构域，其序列与受体蛋白酪氨酸激酶相似，这为提出的各种模型提供了机制。秀丽隐杆线虫的第二个基因，其突变表型是未知的，显示出惊人的序列相似的mes- 1。本课题旨在检测MES-1在早期胚胎中的作用位置和方式，确定MES-1相关蛋白是否参与控制胚胎中的不均匀分裂，并鉴定与MES-1相互作用的其他蛋白，哪些可能是MES-1的配体或靶分子。目的1:MES-1蛋白的分子分析和定位。目的2:mes-1样基因msl-1的分子和表型分析。目的3：鉴定与MES-1一起控制不均匀分裂的其他蛋白。

Strome 9630952 Asymmetric cell divisions generate daughter cells with different developmental fates. This proposal investigates how maternally-supplied factors control asymmetric divisions in the early C. elegans embryo. The maternal-effect gene, mes- 1, plays a crucial role in promoting the unequal divisions that generate somatic founder cells and the germ lineage. The progeny of mes-1 mothers are sterile, due to a transformation of the primordial germ cell, P4, into a muscle precursor, like its somatic sister cell, D. The underlying cause of this cell fate transformation is loss of spindle asymmetry and defective cytoplasmic partitioning in the cells that generate P4 and D. Dr. Strome's studies of the mutant phenotype have suggested several models for how MES-1 participates in promoting unequal divisions and unequal partitioning in embryonic cells. MES-1 contains a putative transmembrane domain and shows sequence similarity to receptor protein-tyrosine kinases, which suggests a mechanism for the various models proposed. A second C. elegans gene, whose mutant phenotype is unknown, shows striking sequence similarity to mes-l. This proposal is to test where and how MES-1 functions in the early embryo, to determine whether the MES-1-related protein participates with MES-1 in controlling unequal divisions in the embryo, and to identify other proteins that interact with MES-1 and which may be ligands or target molecules for MES-1. Aim 1: Molecular analysis and localization of the MES-1 protein. Aim 2: Molecular and phenotype analysis of the mes-1-like gene, msl-1. Aim 3: Identification of other proteins that function with MES-1 In controlling unequal divisions.