Poster abstracts
Poster number 21 submitted by Leanne Kelley
Uncovering variations in conserved signal transduction pathways: the case of the EGFR pathway in Caenorhabditis vulval development
Leanne H. Kelley (Molecular Genetics, Ohio State University), Marcos Corchado (Molecular Genetics, Ohio State University), Abdulrahman M. Jama (Molecular Genetics, Ohio State University), Helen M. Chamberlin (Molecular Genetics, Ohio State University)
Abstract:
With conserved signal transduction pathways serving as the framework for evolution, it is the modifications to these conserved networks that give rise to morphological diversity across species (Mahalak et al. 2017). One such conserved signal transduction network is the EGFR pathway, which regulates vulval development in Caenorhabditis. C. elegans and C. briggsae share much of their morphology and development, despite diverging ~30 million years ago (Sharanya et al. 2015). While the phenotypic vulval cell patterning remains invariant between C. elegans and C. briggsae, genetic variation is evident when the EGFR pathway is perturbed. For example, Cel-sur-2/MED23 mutants are vulvaless, while Cbr-sur-2/MED23 mutants can exhibit normal vulval development (Mahalak et al. 2017). This suggests a compensatory process in C. briggsae that can promote vulval cell patterning when the EGFR pathway is blocked. To identify this compensatory mechanism, we aim to investigate differences in vulval development between C. elegans and C. briggsae by creating mirror mutations based on known gain- and loss-of-function mutations in the EGFR pathway. To date, differences in phenotype between the species have been identified in two genes, spr-4 and htz-1, with C. briggsae mutants exhibiting vulval cell hyperproliferation, while C. elegans mutants show normal vulval cell differentiation (Sharanya et al. 2015). Rescue experiments suggest that Cbr-htz-1 functions cell non-autonomously to regulate vulval cell fate, suggesting that these genes may increase lin-3/EGF transcription. RNA-seq data shows that lin-3/EGF is upregulated in Cbr-htz-1 mutants, but is downregulated in Cel-htz-1 mutants. htz-1’s influence on lin-3/EFG regulation and its role in transcription suggest a role as a synthetic multivulvae (SynMuv) gene, a group of genes that negatively regulate vulval cell patterning in a redundant manner. Uncovering genetic variations within the EGFR pathway between C. elegans and C. briggsae will ultimately broaden our understanding of flexibility in signal transduction pathways over the course of evolution.
References:
Mahalak, K.K., Jama, A.M., Billups, S.J., Dawes, A.T., and Chamberlin, H.M. 2017. Differing roles for sur-2/MED23 in C. elegans and C. briggsae vulval development. Development Genes and Evolution 227, 213-218.
Sharanya, D., Fillis, C.J., Kim, J., Zitnik E.M. Jr,. Ward, K.A., Gallagher, M.E., Chamberlin, H.M., and Gutpa, B.P. 2015. Mutations in Caenorhabditis briggsae identify new genes important for limiting the response to EGF signaling during vulval development. Evolution and Development 17, 34-48.
Keywords: Caenorhabditis, signal transduction pathway, evolution