Event Title

Identifying A Potential New Fgf Receptor Signaling Component In C. Elegans

Location

Lobby in front of Auditorium

Start Date

19-4-2019 11:00 AM

Department

Biology

Description

Fibroblast growth factor receptors (FGFRs) belong to a larger family of receptor tyrosine-kinase (RTK) cell-surface receptors which phosphorylate specific tyrosine residues to trigger downstream responses such as cell proliferation, migration, and differentiation. The study of the EGL-15 FGFR in the nematode Caenorhabditis elegans has long been used as a paradigm to understand principles of RTK signaling, since defects in the processes mediated by EGL-15 result in striking phenotypes that provide powerful genetic tools. One such process is the regulation of fluid homeostasis. EGL-15 hyperactivation causes excessive accumulation of clear fluid inside the worm’s body (the Clear (Clr) phenotype). The isolation of Clr suppressors, termed suppressor of clr (soc) mutants, has led to the identification of many of the core components of EGL-15 signaling. For example, the original set of soc mutations identified the Grb2/SEM-5 adaptor protein that links RTK activation to the activation of the RAS/MAPK pathway. Although SEM-5 is required for EGL-15 signaling, a key component that links activated EGL-15 to SEM-5 has yet to be identified, since an egl-15 mutation, n1457, that eliminates the known SEM-5 binding sites on EGL-15 does not confer a Soc phenotype. To identify these missing components, we conducted a modified “enhancer” Soc screen in an egl- 15(n1457) background. This screen identified new soc mutations, defining up to four new soc genes that potentially function as the additional link between EGL-15 and SEM-5. Of sixteen characterized enhancers, six have been shown to be autosomal. Two are alleles of the known, major soc gene soc-1. Using complementation tests, we have shown that the remaining four autosomal mutations (ay157, ay169, ay174, and ay195) are allelic to one another, and are not alleles of any of the known major soc genes. To demonstrate that this is a novel soc gene, we need to determine whether or not these are alleles of one of the minor soc genes. Genetic mapping experiments can both locate this gene as well as determine whether or not it maps to a region where there are known, minor soc genes. The initial experiments to accomplish this seek to assign this complementation group to a specific chromosome, and we are using ay195 as the representative allele of this complementation group. 2-factor mapping of ay195 has shown that it does not map near the center of either chromosome IV or V. Additional mapping experiments are currently being conducted to determine if ay195 maps to the other chromosomes (I, II, or III). Further characterization of this autosomal complementation group may lead to the discovery of a new autosomal soc gene.

Comments

Michael Stern, Cindy Voisine, and Te-Wen Lo are the faculty sponsors of this poster.

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Apr 19th, 11:00 AM

Identifying A Potential New Fgf Receptor Signaling Component In C. Elegans

Lobby in front of Auditorium

Fibroblast growth factor receptors (FGFRs) belong to a larger family of receptor tyrosine-kinase (RTK) cell-surface receptors which phosphorylate specific tyrosine residues to trigger downstream responses such as cell proliferation, migration, and differentiation. The study of the EGL-15 FGFR in the nematode Caenorhabditis elegans has long been used as a paradigm to understand principles of RTK signaling, since defects in the processes mediated by EGL-15 result in striking phenotypes that provide powerful genetic tools. One such process is the regulation of fluid homeostasis. EGL-15 hyperactivation causes excessive accumulation of clear fluid inside the worm’s body (the Clear (Clr) phenotype). The isolation of Clr suppressors, termed suppressor of clr (soc) mutants, has led to the identification of many of the core components of EGL-15 signaling. For example, the original set of soc mutations identified the Grb2/SEM-5 adaptor protein that links RTK activation to the activation of the RAS/MAPK pathway. Although SEM-5 is required for EGL-15 signaling, a key component that links activated EGL-15 to SEM-5 has yet to be identified, since an egl-15 mutation, n1457, that eliminates the known SEM-5 binding sites on EGL-15 does not confer a Soc phenotype. To identify these missing components, we conducted a modified “enhancer” Soc screen in an egl- 15(n1457) background. This screen identified new soc mutations, defining up to four new soc genes that potentially function as the additional link between EGL-15 and SEM-5. Of sixteen characterized enhancers, six have been shown to be autosomal. Two are alleles of the known, major soc gene soc-1. Using complementation tests, we have shown that the remaining four autosomal mutations (ay157, ay169, ay174, and ay195) are allelic to one another, and are not alleles of any of the known major soc genes. To demonstrate that this is a novel soc gene, we need to determine whether or not these are alleles of one of the minor soc genes. Genetic mapping experiments can both locate this gene as well as determine whether or not it maps to a region where there are known, minor soc genes. The initial experiments to accomplish this seek to assign this complementation group to a specific chromosome, and we are using ay195 as the representative allele of this complementation group. 2-factor mapping of ay195 has shown that it does not map near the center of either chromosome IV or V. Additional mapping experiments are currently being conducted to determine if ay195 maps to the other chromosomes (I, II, or III). Further characterization of this autosomal complementation group may lead to the discovery of a new autosomal soc gene.