hunchback and Ikaros-like Zinc Finger Genes Control Reproductive System Development in Caenorhabditis elegans.

摘要

The entire C. elegans somatic reproductive system is generated from two somatic gonadal precursor (SGP) cells. The SGPs are specified during embryogenesis from the developing mesoderm and migrate to meet two primordial germ cells (PGCs). The SGPs and the PGCs form a four-cell gonad primordium that remains undivided until the L1 larvae hatches from its egg. Each L1 SGP is a multipotent blast cell that has the potential to generate all five tissues of the somatic reproductive system: one distal tip cell (DTC), one anchor cell (AC), dorsal uterine (DU) cells, ventral uterine (VU) cells, and sheath/spermathecae (SS) cells. When combined with a PGC one SGP can generate a self-fertilizing gonad arm complete with sperm, eggs, and embryos. Investigating C. elegans SGP specification and differentiation, therefore, provides an excellent system to understand the molecular mechanisms underlying lineage progression.;Two conserved transcription factors have been previously characterized in early SGP development. The C2H2 zinc finger GLI ortholog tra-1 was found to control late SGP division and polarity whereas the bHLH dHand ortholog hnd-1 was found to control early SGP survival. These investigations lead to the identification of the novel C2H2 zinc finger gene ehn-3, which interacts genetically with either tra-1 or hnd-1 to cause a nearly complete loss of gonad arms.;This dissertation focuses on the characterization of ehn-3 using a variety of techniques. A combination of bioinformatics, genetic interactions, phenotypic characterization, and chimeric rescue constructs indicates ehn-3 is part of a previously unrecognized gene family similar to mammalian Ikaros and Drosophila hunchback; both of which are involved in lineage progression. An RNAi screen was used to search for genes upstream, downstream, and in parallel to ehn-3. Several chromatin factors known to physically interact with either Drosophila hunchback or mammalian Ikaros were discovered to genetically interact with ehn-3. Additional analyses provide support for a model where two chromatin remodeling complexes, SWI/SNF and NuRD, are acting in parallel with or antagonistically to ehn-3 to control SGP lineage progression. This work, in turn, provides the starting point for an understanding of how hunchback and Ikaros-like genes control SGP lineage progression utilizing chromatin factors.