Molecular genetic analysis of reproductive system development in nematodes C. elegans and C. briggsae

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Formation of tissues and organs in metazoans involve dynamic changes in the expression of many genes. How these genes are regulated and what impact changes in their expression have on the organism are not well understood. The nematode (worm) Caenorhabditis elegans and its close relative C. briggsae offer many advantages to study gene regulation and function during development. These two model organisms possess many convenient features and provide powerful molecular and genetic tools to explore biological phenomena that occur in all eukaryotes. In spite of their superficially similar morphology, the genomes of C. elegans and C. briggsae show significant differences in both coding and non-coding regions. This provides a unique opportunity to investigate alterations in genes and pathways over time without obvious changes in structure. This process, termed developmental system drift (DSD), is the evolutionary change in genetic mechanisms that underlie crucial and invariant phenotypes. To study the mechanisms of organ formation and DSD my laboratory is conducting a comparative analysis of reproductive system development, specifically the vulva, in these two nematodes. The vulva is a mating structure in female worms (hermaphrodites) that is normally composed of 22 cells. Notwithstanding its simplicity, the system exhibits functional complexities that are, in many ways, comparable to human organs. We have isolated a large number of C. briggsae vulva mutants with aberrant phenotypes including Vul (vulvaless, fewer cells), Muv (multivulva, more cells), and Pvl (protruding vulva, abnormal invagination). Similar phenotypic classes in C. elegans have led to a comprehensive understanding of conserved signaling pathways (e.g., Ras) and transcriptional networks that control organ formation. Our published work has shown that the roles of some of the C. briggsae vulva genes, such as Cbr-lin-11/LIM-HOX and Cbr-pry-1/Axin, have diverged from C. elegans (see [1, 2]). Recently we have found that Muv-class genes also show interesting differences. In some cases animals exhibit a vulval induction pattern that is not observed in any of the known C. elegans Muv mutants, demonstrating that vulval development in C. briggsae is orchestrated by diverged mechanisms. To pursue comparative study of vulva development we will use a range of approaches in classical genetics, molecular biology, bioinformatics, and combine them with cutting-edge technologies including SNP-chip polymorphism mapping and next-generation sequencing. Our results promise to uncover some of the changes in gene networks that specify morphological and developmental diversity in animals. The findings will advance our knowledge in areas of developmental and evolutionary biology. The proposed research projects will generate highly-qualified personnel (HQP) with a broad range of training in genetics, cell biology, computational biology, imaging and transgenics. These skills are needed to support Canadian biomedical science and the acquired experience will make HQP suitable in academia, industry and government jobs.