The C. elegans germline is a polar tissue with distal cells mitotically dividing, while more proximal cells enter meiosis and differentiate into gametes. Results from biochemical and genetic studies indicate that the GLP-1/Notch signaling pathway promotes distal germ cell proliferation by antagonizing two redundant pathways, one containing GLD-1 and the other GLD-2, which each promote meiotic entry (1-3). Two genetic screens were performed to identify novel genes involved in regulating the proliferation vs. differentiation decision. In one screen, mutations that enhanced the over-proliferation phenotype of a weak
glp-1(
oz112oz120 gf) allele were identified. In the other screen, mutations that were synthetic tumorous with a
gld-2 null allele were isolated. As a result,
teg-1 (tumours enhancer of
glp-1(gf)) was identified in both screens. The open reading frame of
teg-1 encodes a protein of 370 amino acid residues. TEG-1-related proteins are found from yeast to human and contain GYF domain that is thought to play a role in protein-protein interactions (4). We have raised antibodies against TEG-1 peptides, which detect a band at about 65 kDa in N2 lysate, but not in a
teg-1 null mutant lysate, indicating the antibodies are specific to TEG-1. Subcellular localization studies demonstrate that TEG-1 is found in all germline and somatic nuclei of the gonad, with stronger staining being detected in distal tip cell, proximal germ cells, and oocytes. Moreover, we found that TEG-1 co-immunoprecipitates with UAF-1, the large subunit of U2 small nuclear ribonucleoparitcle (snRNP) auxiliary factor (5), suggesting TEG-1 forms a complex with a subset of UAF-1. This finding is reminiscent the human TEG-1 homolog CD2BP2, which interacts with a tri-snRNP bridging protein that is a component of the spliceosome complex (6), and suggests C. elegans TEG-1 may also involve in pre-mRNA splicing. We are currently conducting experiments to identify potentially misspliced mRNAs in
teg-1 mutants to better understand the mechanism of TEG-1in regulating the proliferation vs. meiotic entry decision in the germ line. 1. Hubbard, E.J. 2007. Dev. Dyn. 236: 3343-3357. 2. Kimble, J. and S.L. Crittenden. 2007. Annu. Rev. Cell Dev. Biol. 23:405-33. 3. Hansen, D. and T. Schedl. 2006. Curr. Top. Dev. Biol. 76:185-215. 4. Kofler, M.M. and C. Freund. 2006. FEBS J. 273:245-256. 5. Zorio, D.A. and T. Blumenthal. 1999. Nature 402:835-838. 6. Laggerbauer. B. et. al. 2005. RNA 11:598-608.