Inductive cell-signaling in the gonad; the regulation of Notch-type signaling
In C. elegans, as in other animals, Notch-type signaling mediates many inductive events during development. The mechanism of Notch-type signaling involves proteolytic cleavage of the receptor and subsequent transport of the receptor intracellular domain to the nucleus, where it acts as a transcriptional regulator. Notch-type signaling activity is modulated by post-translational modifications and endocytosis of ligand and receptor. The C. elegans genome encodes two Notch-type receptors, GLP-1 and LIN-12, which are active in a variety of cell-signaling events in the embryo, larva, and adult.
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Germline proliferation (MZ, mitotic zone) is maintained in 99% of glp-1(bn18) and 100% of ego-2(RNAi) adults under the assay conditions used. In contrast, when both glp-1 and ego-2 activities are reduced, germline proliferation ceases during early larval development in 44% of double mutants; adults contain only a few sperm (arrowheads). TZ, transition zone (early 1st meiotic prophase); PZ, pachytene zone; sp, sperm; arrows, oocyte nuclei.
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We identified the ego-2 (enhancer of glp-1) gene as a positive regulator of germline proliferation that interactsgenetically with the GLP-1/Notch signaling pathway in the germ line (Qiao et al. 1995). We subsequently found that ego-2 positively regulates signaling in various tissues via both GLP-1/Notch and LIN-12/Notch. ego-2 activity also promotes aspects of development not known to require GLP-1 or LIN-12 (Liu and Maine 2007).
The EGO-2 protein contains a Bro1 domain, which is known in other systems to localize to certain endosomal compartments (Liu and Maine 2007). Hence, we hypothesize that EGO-2 may function as an endosomal protein. EGO-2 activity in the soma promotes GLP-1 signaling in the germ line, consistent with a role for EGO-2 in production of active ligand by the signaling cell. Another C. elegans Bro1-domain protein, ALX-1, is known to interact physically with LIN-12/Notch. We found a complex pattern of genetic interactions between the ego-2 and alx-1 genes, consistent consistent with their relationship being antagonistic with respect to some developmental processes and agonistic with respect to others.
The focus of our current work is to determine the subcellular localization of EGO-2 protein (i.e., is it endosomal as predicted?) and to identify proteins that interact with EGO-2 to promote Notch-type signaling.
Selected Related Publications:
Liu,Y., and E.M. Maine (2007) The Bro1-domain protein, EGO-2, promotes Notch signaling in Caenorhabditis elegans. Genetics 177, 2265-227. [PDF]
Qiao, L., J.L. Lissemore, P. Shu, A. Smardon, M. Gelber, and E.M. Maine (1995) Enhancers of glp-1, a gene required for cell-signaling in C. elegans, define a set of genes required for germline development. Genetics 141, 551-569. [PDF]
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