Research Interests

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 epithelial ("hypodermal") cells which, in males only, fuse very late in juvenile ("larval") development and change their cellular structure and position.  This results in a blunt ("peloderan") shape (the pointy shape of the hermaphrodite tail results from lack of morphogenetic change).  We have completed a transmission electron microscopic reconstruction of these cellular events, providing a foundation for functional studies.  We have isolated mutations in various genes that fail at certain steps of male tail tip morphogenesis and we are cloning the genes identified by these mutations to understand their molecular functions.  One of these genes acts downstream of a Wnt signaling pathway to determine fates of posterior daughter cells of asymmetric cell divisions.  A second gene acts in the "heterochronic" pathway, downstream of the let-7 microRNA to determine appropriate timing of morphogenesis.  Using RNAi, we will systematically test for other genes in the genome required for morphogenesis.  We are also using laser microsurgery to test hypotheses about the involvement of particular cells in signal transduction events required for morphogenesis.

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.