The Wightman lab is studying the molecular mechanism of uterus development in the nematode worm, Caenorhabditis elegans. The study provides a model for understanding how organs develop in all animal species. Evolutionary changes in animal morphology are caused in large part by modifications in the underlying developmental programs of organisms. The functions of key developmental regulatory genes have been conserved over many phyla, yet the same pathways have been modified to different purposes in different organisms. The Wightman lab is studying how the function of an evolutionarily- conserved gene, nhr-67, has been adopted to a new function in uterus organogenesis in the nematode C. elegans. There are equivalent genes in most, if not all, animals, including humans and flies, where the gene is named tailless. In vertebrates, the tailless gene functions in neural stem cell development. Like tailless, the product of the nhr-67 gene is expected to control animal development by regulating the transcription of other genes in various cells. The uterus of C. elegans is created by a cell-cell signaling process in which the anchor cell (AC) plays a primary organizing function. The AC signals to six adjacent uterine cells (pi cells) to induce their division and differentiation into twelve specialized uterine cells. When development of the uterine cells is disrupted due to mutations in the nhr-67 gene, animals are unable to lay eggs. The Wightman lab is using molecular genetic, and both light and electron microscopic approaches to assess the nature of nhr-67 function in uterus development. This research program has three primary specific aims: 1) Determine the nature of pi lineage and uterine defects due to mutations in nhr-67, 2) Determine in which cells the nhr-67 gene functions, and 3) Understand the function of the nhr-67 gene product in the AC to pi cell signaling pathway. This project also serves major educational goals. Most of the proposed work is being performed at Muhlenberg College, a liberal arts institution that has no graduate students. Undergraduates and exceptional high school students, supervised by three senior personnel, perform most of the research. Students participate in all aspects of experimental design, execution, interpretation, and dissemination. Therefore, this project helps foster a local "culture of science" that enlivens undergraduate science education at Muhlenberg College.
