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.
