Poster abstracts
Poster number 27 submitted by Leanne Kelley
Tumor suppressor genes in vulval development reveal cryptic genetic variation between C. elegans and C. briggsae
Leanne H. Kelley (Department of Molecular Genetics, Ohio State University), Marcos Corchado (Department of Molecular Genetics, Ohio State University), Abdulrahman M. Jama (Department of Molecular Genetics, Ohio State University), Helen M. Chamberlin (Department of Molecular Genetics, Ohio State University)
Abstract:
The EGFR/Ras/MAPK pathway, which is conserved across metazoans, is an important regulator of cell proliferation. Defects in this pathway are hallmarks of some cancers, such as melanoma. Our research uses Caenorhabditis vulval development as a model to enhance our understanding of the mechanisms that govern regulation in the EGFR/Ras/MAPK pathway. A recent study has identified four prospective tumor suppressor genes in C. briggsae that inhibit vulval cell hyperproliferation, indicated by the presence of the multivulva (Muv) phenotype when these genes are altered (Sharanya et al. 2015). Whole-genome sequencing has identified the C. briggsae Muv genes as Cbr-spr-4, Cbr-gon-14, Cbr-htz-1, and CBG03376. Given that the Muv genes encode nuclear proteins, it is hypothesized that these genes regulate vulval development by altering the transcription of other genes. Rescue experiments suggest that Cbr-htz-1 functions cell non-autonomously to regulate vulval cell fate, leading us to hypothesize that these genes may increase the transcription of the ligand gene lin-3/EGF. However, qRT-PCR data does not show an increase in lin-3/EGF transcript abundance for the C. briggsae Muv mutants, while RNA-seq data for two of the C. briggsae Muv mutants show an increase in lin-3/EGF transcription abundance. lin-3 RNAi knockdown experiments may further clarify whether these C. briggsae Muv mutants regulate vulval development through lin-3/EGF. In efforts to determine if these genes similarly impact the EGFR/Ras/MAPK pathway in C. elegans, mutant C. elegans lines have been established for three of the four Muv genes. Two of these mutant lines (Cel-gon-14 and Cel-htz-1) confer a Muv phenotype, while the mutant Cel-spr-4 line does not. Uncovering cryptic genetic variations within vulval development between C. briggsae and C. elegans will ultimately broaden our understanding of nematode vulval development and the role of tumor suppressors in EGFR/Ras/MAPK pathway regulation.
References:
Sharanya, D., Fillis, C.J., Kim, J., Zitnik, E.M., Jr., Ward, K.A., Gallagher, M.E., Chamberlin, H.M., and Gupta, B.P. 2015. Mutations in Caenorhabditis briggsae identify new genes important for limiting the response to EGF signaling during vulval development. Evolution & Development 17:1 34-48.
Keywords: Caenorhabditis, tumor suppressor