Talk abstracts
Talk on Wednesday 04:15-04:30pm submitted by Karley Mahalak
Using sur-2 as a gateway to understanding EGF pathway interaction differences in nematodes
Karley K. Mahalak (MCDB), Edward Zitnik (Molecular Genetics), Helen Chamberlin (Molecular Genetics, OSU)
Abstract:
The EGF/Ras signaling pathway is essential for the proper development of most multicellular animals. We are studying the function of the EGF pathway in the context of vulval development in the Caenorhabditis genus of nematodes to better understand the evolutionary flexibility and constraints imposed by signaling pathways on the regulatory networks in which they participate. Normal vulval development in the related species C. elegans and C. briggsae is essentially identical. However, the EGF pathway is essential for vulval cell fate in C. elegans, but not C. briggsae. Specifically, when the EGF pathway is disrupted by a MEK inhibitor (U0126), all of the vulval precursor cells (VPCs) of C. elegans fail to become vulval cells, whereas in C. briggsae, some VPCs still differentiate into vulval cells. We have likewise identified differences between the species in the sur-2 gene. sur-2 encodes the Med23 component of the transcriptional Mediator complex, and acts downstream of EGF signaling in C. elegans, mammals, and other animals. In C. elegans vulval development, sur-2 serves as the link between the EGF/Ras and Notch pathways. Cel-sur-2 mutants exhibit reduced vulval development, and frequently lack the cells that comprise the sides of the vulva (the secondary cells) due to a failure to express LAG-2, a ligand for Notch. In contrast, we have identified a Cbr-sur-2 mutant strain, and found that they have normal levels of vulval development, and an overproduction (rather than loss) of secondary fated cells. To reconcile these phenotypic differences, we have used molecular markers to interpret the cell fate choices in C. elegans and C. briggsae sur-2 mutants. We find that mutants for both species are similar in that they are deficient in the development of primary cells (cells that normally form the apex of the vulva). The species differ on whether this defect interferes with the production of the lateral secondary cells. We interpret that the differences in sur-2 mutants uncovers a key distinction between the species with respect to the connection between EGF/Ras and Notch signaling, and in the importance of EGF signaling in promoting the secondary cell fate.
Keywords: EGF pathway, Mediator Complex