Variation in EGF/Ras signaling in C. elegans and C. briggsae vulval development
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Date
2014-05
Authors
Zitnik, Edward
Journal Title
Journal ISSN
Volume Title
Publisher
The Ohio State University
Abstract
The EGF/Ras signal transduction pathway has been shown to be essential in nematode vulval development. When levels of EGF signal are manipulated, precursor cells that give rise to the adult vulva (egg-laying structure) have different division patterns. When EGF/Ras is overactive, the precursor cells experience extra divisions. These extra cellular divisions model tumor growth. Individuals in the human population have varying sensitivities to mutations in this pathway and modern chemotherapy treatments attempt to individualize treatment to account for these differences. To further model this variance, we examine the vulva development system in two species of nematode, C. elegans and C. briggsae. Like two patients both presenting with tumors, these two species both develop extra cellular divisions from hyperactive EGF/Ras signaling, yet they react differently when treated with drug therapies. I have completed three experiments which show the variation across the two species to U0126, a small molecule inhibitor of mitogen-activated protein kinase kinase (MEK), which acts in the EGF/Ras pathway. The first is a dose response experiment on wild-type animals which shows a complete elimination of vulva development in C. elegans but only a partial reduction in development in C. briggsae. The second is a drug treatment of nematodes with an extra cell division phenotype which shows elimination of the phenotype in C. elegans and a reduced—yet still present—proportion of animals expressing the phenotype in C. briggsae. The third experiment exposes the mutant sur-2, a downstream component of the EGF/Ras pathway, to the inhibitor and shows complete elimination of precursor cell division in C. elegans, and only a marginal decrease in division in C. briggsae. The results of these three experiments suggest that the vulval development process in C. briggsae is less sensitive to EGF signaling than in C. elegans and C. briggsae may rely on alternative signaling sources to develop the vulval tissue.
Description
2014 Denman Undergraduate Research Forum, 3rd place
Keywords
vulval development, C. elegans, C. briggsae, EGF, Ras