We are studying tubulogenesis of the C. elegans foregut or pharynx to understand morphogenesis of the digestive tract. The pharynx primordium is initially organized as a cyst. During pharyngeal elongation, the cyst is reorganized into a short epithelial tube connected to the exterior environment by the arcade cells and anterior epidermis. I have initiated a study of pharyngeal morphogenesis by focusing on a mutant of the phe-1 gene in which the pharynx fails to attach to the arcade cells and remains cyst-like. I have identified three defects in phe-1 embryos: 1) whereas anterior pharynx cells normally reorient their apical membranes to become aligned with the arcade cells, the anterior pharyngeal cells do not reorient their apical membranes in phe-1 mutants; 2) arcade cells are frequently mislocalized within the embryo and fail to generate an epithelium; 3) the basement membrane surrounding the pharynx is not remodeled as it is in wild-type embryos. The goal of this proposal is to understand the role of phe-1 in pharyngeal elongation. I will characterize the phenotype of phe-1 mutants, I will clone the phe-1 locus and I will initiate a molecular characterization of phe-1. I anticipate that phe-1 could be involved in cell fate specification of pharyngeal cells, arcade cells or anterior epidermis. Alternatively, phe-1 could be involved more directly in the cell biology of pharyngeal elongation. I have chosen the simple model organism C. elegans because of its powerful experimental advantages. Genes can be quickly identified and ordered into molecular pathways. C. elegans is transparent and there are only 80 cells in the mature pharynx. Therefore pharynx elongation can be studied in living embryos and on a single cell basis. The complete genome sequence is available and is amenable to rapid gene inactivation. My ultimate goal is to apply what I learn in C. elegans to the morphogenesis of the mammalian digestive tract. C. elegans pharynx elongation shares some features with kidney tubulogenesis. Thus, understanding C. elegans pharynx morphogenesis may provide insights into similar events in higher organisms. My experience in Dr. Mango's lab learning C. elegans methodologies will complement my prior training in mouse genetics with Drs. Jeffrey Gordon and Shirley Tilghman. The Huntsman Cancer Institute will provide a vibrant research environment with faculty members in many fields including C. elegans biology, development, cell biology and genetics. I am mentored by C. elegans biologist Dr. Susan Mango and cell biologist Dr. Mary Beckerle.
| Jenkins, Noah; Saam, Jennifer R; Mango, Susan E (2006) CYK-4/GAP provides a localized cue to initiate anteroposterior polarity upon fertilization. Science 313:1298-301 |
| Han, Zhenbo; Riefler, Gary M; Saam, Jennifer R et al. (2005) The C. elegans Tousled-like kinase contributes to chromosome segregation as a substrate and regulator of the Aurora B kinase. Curr Biol 15:894-904 |
| Portereiko, Michael F; Saam, Jennifer; Mango, Susan E (2004) ZEN-4/MKLP1 is required to polarize the foregut epithelium. Curr Biol 14:932-41 |
| Han, Zhenbo; Saam, Jennifer R; Adams, Henry P et al. (2003) The C. elegans Tousled-like kinase (TLK-1) has an essential role in transcription. Curr Biol 13:1921-9 |
