Biography
Our broad goal is to understand the regulation of animal development at the molecular level. We are particularly interested in controls of cell fate and patterning within multicellular tissues. Our experimental approach relies on the powerful genetics, simple anatomy and complete genome sequence of the nematode C. elegans. This model organism provides a way to identify and analyze regulators that are used throughout the animal kingdom for basic processes of development. Our work concerns three primary areas:
Signal transduction and regulation of proliferation:
Cells signal back and forth to each other during development to control growth, differentiation and pattern. We have identified the core components of a signal transduction pathway that regulates induction of the germ line tissue: (1) the GLP-1 membrane receptor, (2) the LAG-1 DNA binding protein, (3) the LAG-2 signaling ligand, and (4) the LAG-3 co-activator. We are exploring how this signaling pathway controls growth and differentiation of the germline tissue.
Translational control and controls of cell fate:
Messenger RNAs are commonly controlled during germline development and early embryogenesis at the translational level. In collaboration with Dr. Marvin Wickens, we used the yeast three-hybrid system to identify a trans-acting regulator that acts through the 3? untranslated region of fem-3 mRNA to control the decision between spermatogenesis and oogenesis. The regulator is called FBF, for fem-3 binding factor. FBF is encoded by two gene, fbf-1 and fbf-2, and is homologous to the Drosophila translational regulator known as Pumilio. We are currently asking how FBF and other Pumilio-related proteins in C. elegans regulate germline development.
Organogenesis:
Organs are generated from groups of cells that work together to complete the complex functions of the organ. We have conducted mutagenesis screens to identify genes that control assembly of the four-celled gonadal primordium and development of that primordium to generate either a hermaphrodite symmetrical or a male asymmetrical gonad. Our goals are to learn how organ polarity is established and how epithelial tissues are regulated to generate individual substructures within an organ.
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