PIE-1, MEX-5, MEX-6, and soma/germline asymmetry in C. elegans embryos

Abstract

The separation between soma and germline in C. elegans embryos occurs through a series of asymmetric cell divisions initiating with the 1-cell stage. Each of these divisions results in one daughter that will produce only somatic cells, called a somatic precursor. The other daughter will produce germ cells in addition to somatic cells and is called a germline precursor.Each germline precursor contains, but does not respond to, factors that promote somatic differentiation. This property requires the maternal gene pie-1; mutations in pie-1 result in the germline precursors adopting somatic cell fates. In the first part of this thesis I describe the immunolocalization of PIE-1. I show that PIE-1 is predominantly a nuclear protein, localized exclusively to each germline precursor. The localization of PIE-1 contributes to data that suggest PIE-1 functions in each germline precursor to prevent the transcription or accumulation of embryonically transcribed mRNAs.PIE-1 belongs to a group of proteins, called germline proteins, that localize to germline precursors. In the second part of this thesis I describe my work on two highly related genes, mex-5 and mex-6 , that have high sequence similarity and appear to function directly in localizing PIE-1 and other germline proteins. Embryos lacking mex-5/mex-6 show uniform expression of germline proteins and other classes of proteins required for the identities of early blastomeres. I provide evidence that MEX-5/MEX-6 inhibits the expression of germline proteins; MEX-5 is a novel, cytoplasmic protein, localized in a pattern reciprocal to that of the germline proteins, and ectopic expression of MEX-5 is sufficient to inhibit the expression of germline proteins.I show that MEX-5 expression is dependent on a group of cortical proteins (PAR proteins) that are asymmetrically distributed as early as the 1-cell stage; anterior PAR proteins associate with the anterior cortex, and posterior PAR proteins associate with the posterior cortex of the egg. I show that MEX-5 localization requires both an anterior and a posterior PAR protein, and provide evidence that MEX-5/MEX-6 link asymmetries in the expression of the PAR proteins to asymmetries in proteins, like PIE-1, that specify the fates of somatic and germline precursors.