MOLECULAR GENETIC STUDY OF REPRODUCTIVE SYSTEM DEVELOPMENT IN THE NEMATODE CAENORHABDITIS BRIGGSAE

Abstract

The nematode C. briggsae, a relative of C. elegans, is a widely used animal model for comparative studies to understand evolution of gene function and developmental mechanisms. To investigate differences in the mechanism of reproductive system development, genetic screens were conducted in our laboratory to isolate C. briggsae mutant strains that display abnormal vulva and vulva-uterine connection. The screens yielded at least seven genes whose loss of function results in a multivulva phenotype and 13 genes that result in egg-laying defective and protruding vulva phenotypes. Molecular cloning experiments were carried out to determine the identities of these genes, leading to the identification of five C. elegans orthologs that function at different steps of vulval development process. Three of these, Cbr-lin-1, Cbr-lin-31 and Cbr-pry-1, encode components of Ras and Wnt pathways. The remaining genes are uncloned and include novel regulators of C. briggsae vulval development. Our comparative study of vulval development in C. briggsae and C. elegans has revealed differences in three homologous processes – inter-VPC distance, fate specification and anchor cell migration. Together these studies demonstrate that despite the overall similarity in vulval cell numbers and morphology between the two Caenorhabditis species, the underlying genetic programs include both conserved and divergent functional components. Additionally, this work highlights key resources such as mapping tools, mutant strains and CRISPR genome editing technology that have been developed to facilitate the use of C. briggsae in a comparative and individual context.