Our work focuses on understanding the molecular processes underlying organogenesis. Organs are an important functional level of organization for cells within animals. Within an organ, cells of different types coordinate their development, and proper development is critical for normal function. In humans, defects in organ development underlie a variety of birth defects, and mutations in genes important for normal organogenesis are associated with tumors. Thus, understanding fundamental aspects of organogenesis can provide insight into human disease. Important questions in organogenesis include 1) what processes and molecules make cells within an organ different from each other, and 2) what makes cells within an organ different from other cells in the animal.

We use genetic, cell biological and molecular approaches to study the development of the C. elegans hindgut as a model for organogenesis. The hindgut is a simple organ comprised of only eleven cells (eight different cell types), so its development can be studied at the resolution of single cells. In genetic screens for mutants we have identified and characterized several genes that play a role in hindgut development.
Current work focuses on a set of three genes important for making cells within the hindgut different from each other. These genes encode three different types of transcription factors: a Pax, a T-box and a zinc finger protein. Two important questions are 1) what are the signal transduction pathways that regulate the activity of these factors, and 2) what are the target genes regulated by these factors.
We are using a combination of traditional genetic screens and systematic analysis of the fully sequenced C. elegans genome to address these questions. One exciting observation is that the Pax factor (called EGL-38) provides a link between the processes that make the cells within the hindgut different from each other and the processes that make them different from other cells in the animal. Specifically, we have found EGL-38/Pax regulates the expression of both the zinc finger protein (required to make cells different, above) and a cadherin (a cell adhesion molecule) expressed by cells in the hindgut but not in their neighbors outside the organ. Because these molecules are conserved between nematodes and mammals, our work with C. elegans can identify new genes and processes that are fundamental to animal organ development.