Morphogenesis and evolution of development in C. elegans
We are interested in how diversity of biological form is produced through evolutionary changes in genes and developmental processes.
1. Developmental genetics of epithelial morphogenesis
Using the developmental genetic model system Caenorhabditis elegans, we are discovering genes and mechanisms responsible for morphogenesis. C. elegans is complex enough to share components and mechanisms of multicellular animals, but is simple enough to be described in complete terms. As a model biological form, we study the sexually dimorphic tail tip. This simple feature is constructed of only four epidermal cells which—in males only—fuse during postembryonic development and change their cellular structure and position. This results in a rounded ("peloderan") shape in males; the pointed shape of the hermaphrodite tail results from lack of morphogenesis. We have completed a genome-wide RNAi screen, which identified 212 genes involved in tail tip morphogenesis. Using GFP (green fluorescent protein) reporters and fusions, we are deteriming the expression patterns for these genes and interactions between these genes. Emerging from these studies is a picture of the genetic architecture regulating morphogenesis. Excitingly, these studies also reveal the downstream components of the cell-biological machinery involved in morphogenesis, allowing for the first time a means to uncover all the connections between regulators and effectors in this important but complex process. We are also using laser microsurgery to isolate tail tips and profile the dynamic changes to the transcriptome using microarrays and RNAseq.
2. Evolution of male tail diversification
Evolutionary changes have also occurred to produce tail tip morphological diversity in species related to C. elegans (nematode family Rhabditidae). Some species have males that bear conical, pointed, "leptoderan" tail tips that result from a failure in morphogenesis, similar to several of the mutations we isolated in C. elegans. Using molecular phylogenetic analysis in combination with developmental profiling, we are reconstructing the developmental changes that have occurred in male tails during the evolution of family Rhabditidae. So far, we have found several mutations that closely mimic evolutionary changes, suggesting candidate genes that could have been involved. These evolutionary hypotheses are testable, for example, by interspecific transformation using reconstructed ancestral molecules. Not only will these investigations provide specific information about the genes and processes conserved in morphogenetic mechanisms, but will also provide insight into the ways that these mechanisms can change to produce variation in multicellular form.