To build organs, embryos have evolved mechanisms that integrate the development of complex populations of cells. Our group studies organ formation using a simple organ, the C. elegans pharynx (or foregut), that nonetheless faces the same hurdles that confront organs in more complicated animals. We combine molecular genetics, genomics and cell biological approaches to address four aspects of organogenesis:
Pluripotency and cell-fate acquisition:
Early embryonic cells are born pluripotent, but over time their developmental choices become restricted. We study the processes that mediate the transition from pluripotency to cell-fate acquisition, with a particular focus on the interplay between sequence-specific transcription factors, chromatin organization and nuclear architecture (Yuzyuk 2009, Kiefer 2007).
Transcriptional logic of organogenesis:
Our previous studies revealed that there are ‘organ selector genes’ that encode transcription factors and specify organ identity. We would like to understand how the pharynx selector gene pha-4 coordinates organ formation in space and time. We are particularly interested in the role of DNA binding affinity for temporal control and promoter priming (Gaudet 2002, 2004, Deplancke 2006, Updike 2006).
Nutrition and post-embryonic development.
Despite its simple organization, the nematode digestive tract is highly responsive to nutrient availability. Worms can adjust their rate of feeding, their energy utilization and, most dramatically, their development and growth. Our goal is to probe how the developmental pathways that govern gut development in embryos are redeployed after birth, to sense and respond to food. (Ao 2006, Sheaffer 2008).
Many organs, including the C. elegans pharynx, are systems of epithelial tubes that provide an essential function by transporting gases or liquids. Epithelial tubes can be formed by remodeling pre-existing sheets of epithelial cells or by constructing tubular epithelia de novo. Nephrons in the kidney are one example of de novo epithelialization, the C. elegans pharynx is another. While significant progress has been made towards understanding the mechanisms that govern folding of epithelial sheets, very little is known about tubulogenesis by de novo epithelialization. In C. elegans, the pharynx tube is formed in the absence of known epithelial regulators such as cadherins, integrins or catenins. A new direction for the lab is to elucidate cadherin-independent epithelial tube formation.