ABSTRACT
In the germ line of the Caenorhabditis elegans hermaphrodite, nuclei either proliferate through mitosis or initiate meiosis, finally differentiating as spermatids or oocytes. The production of oocytes requires repression of the fem-3 mRNA by cytoplasmic FBF and nuclear MOG proteins. Here we report the identification of the sex determining gene mog-3 and show that in addition to its role in gamete sex determination, it is necessary for meiosis by acting downstream of GLP-1/Notch. Furthermore, we found that MOG-3 binds both to the nuclear proteins MEP-1 and CIR-1. MEP-1 is necessary for oocyte production and somatic differentiation, while the mammalian CIR-1 homolog counters Notch signaling. We propose that MOG-3, MEP-1 and CIR-1 associate in a nuclear complex which regulates different aspects of germ cell development. While FBF triggers the sperm/oocyte switch by directly repressing the fem-3 mRNA in the cytoplasm, the MOG proteins play a more indirect role in the nucleus, perhaps by acting as epigenetic regulators or by controlling precise splicing events.
Subject(s)
Caenorhabditis elegans , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans/growth & development , Caenorhabditis elegans/physiology , Co-Repressor Proteins , Germ Cells/metabolism , Glucagon-Like Peptide 1/genetics , Glucagon-Like Peptide 1/metabolism , Male , Meiosis , Oocytes/metabolism , Oocytes/physiology , RNA Splicing , RNA, Messenger/genetics , RNA, Messenger/metabolism , Spermatozoa/metabolismABSTRACT
The switch from spermatogenesis to oogenesis in the Caenorhabditis elegans hermaphrodite requires mog-6, which post-transcriptionally represses the fem-3 RNA. In this study, we show that mog-6 codes for a divergent nuclear cyclophilin, in that a conserved domain is not required for its function in the sperm-oocyte switch. MOG-6 binds to the nuclear zinc finger protein MEP-1 through two separate domains that are essential for the role of MOG-6 in the sperm-oocyte switch. We propose that MOG-6 has a function distinct from that of prevailing cyclophilins and that its binding to MEP-1 is essential for germline sex determination. Finally, we found that gld-3 mog-6 mutants develop germline tumors, suggesting that mog-6 might function in the decision between mitosis and meiosis.
