Talk abstracts

Talk on Saturday 10:50-11:05am submitted by Xin Li

Ephrin signaling acts through Ras/MAPK to promote C. elegans germline cell death

Xin Li (Dept. of Molecular Genetics, The Ohio State University, Columbus OH 43210, USA), Hongtao Jia (Dept. of Molecular Genetics, The Ohio State University, Columbus OH 43210, USA), DonHa Park (Dept. of Molecular Genetics, The Ohio State University, Columbus OH 43210, USA), Ian Chin-Sang (Dept. of Biology, Queens University, Kingston ON K7L 3N6, Canada), Helen M. Chamberlin (Dept. of Molecular Genetics, The Ohio State University, Columbus OH 43210, USA)

Abstract:
Programmed cell death (apoptosis) eliminates unwanted and damaged cells during normal development and physiological homeostasis. The proper regulation of apoptosis is important to animals at all stages. In the C. elegans hermaphrodite gonad, about half of the germ cells undergo apoptosis during gamete formation (referred to as “physiological germline cell death”). Previous studies have shown that Ras/MAPK signaling is required for normal germline apoptosis (Gumienny et. al., Development, 1999 126:1011-1022). However, the upstream trigger that activates C. elegans germline apoptosis is not known. To identify regulators of germline apoptosis that might act through Ras, we surveyed the functions of C. elegans receptor kinase genes expressed in germline. Among five genes tested, we found that only the Eph receptor gene, vab-1, affected germline apoptosis. Loss-of-function mutants of vab-1 display a decrease in germline apoptosis, whereas an activated form of VAB-1 confers an increase in germline apoptosis. Furthermore, we found that genes for two ephrin ligands (efn-1 /vab-2, efn-3) also promote germline apoptosis. Analysis of different vab-1 mutants has shown that the germline apoptosis phenotype is correlated with disruption of kinase activity. We hypothesized that the ephrin ligands and VAB-1 act through Ras/MAPK signaling to regulate germline apoptosis. Consistent with this hypothesis, the increased germline apoptosis conferred by activated VAB-1 is dependent on a functional Ras/MAPK pathway. In addition, we found that Eph receptor and ligands mutatnts exhibit reduced or no MPK-1 protein phosphorylation in the apoptotic region of the worm gonad compared to wild-type animals. Taken together, we propose that VAB-1/ephrin signaling is an upstream trigger that activates the Ras/MAPK pathway to induce physiological germline cell death.

Keywords: Ephrin signaling, C elegans, Apoptosis