Function of Wnt Signaling During C. Elegans Vulval Induction

University Of Maryland Baltimore County, Baltimore MD

Investigators

Abstract

Function of Wnt Signaling during C. elegans Vulval Induction. David M. Eisenmann, University of Maryland Baltimore County Abstract All metazoan organisms rely on the use of extracellular signals to regulate cell division, migration and differentiation during development. Several evolutionarily-conserved signal transduction pathways are used to receive these signals and alter the regulation of genes and proteins that bring about changes in the behavior of responding cells. One of these conserved signaling pathways is the Wnt signaling pathway. Wnt pathways function in vertebrates during the development of the nervous system, the heart, the reproductive organs, and the skeletal system, and other processes. Much of our knowledge of the function of the Wnt pathway has come from genetic, molecular and biochemical analyses in model systems such as Drosophila, Xenopus and C. elegans. This lab has previously shown that Wnt signaling is involved in the development of the vulva of the C. elegans hermaphrodite. During vulval induction, six equivalent vulval precursor cells are instructed to adopt distinct cell fates by the action of extracellular signals that activate receptor tyrosine kinase/Ras and Notch signaling pathways in these cells. Previous work showed that the Wnt pathway acts with the Ras pathway to coordinately regulate the levels of LIN-39, a member of the important class of evolutionarily-conserved transcription factors encoded by Hox genes, and current results indicate that the levels of LIN-39 in the vulval precursor cells play an important role in which cell fate they adopt. The experiments in this proposal aim to further characterize the role of Wnt signaling in vulval induction in C. elegans Specifically, to identify novel factors acting in C. elegans Wnt signaling, the mig-14 gene will be cloned and characterized and suppressors of the mig-14 mutant phenotype will be isolated and characterized. mig-14 is very interesting because mig-14 mutations lead to defects in most processes regulated by Wnt signaling in C. elegans, yet the mig-14 genomic region contains no known Wnt components or regulators. Also, mig-14 is likely to act in the Wnt sending cell, suggesting it could shed light on some of the unknown issues involved ligand production and secretion. Additional Wnt pathway factors may also be identified by proteins which physically interact with the C. elegans b-catenin BAR-1, which will be characterized in this proposed work. To investigate how cells become responsive to Wnt signals, cis- and trans-acting factors that control the BAR-1 expression pattern will be identified. This work will hopefully identify novel Wnt pathway components and regulators, and extend our knowledge of this important evolutionarily-conserved signaling pathway.