A novel member of the tob family of proteins controls sexual fate in Caenorhabditis elegans germ cells.
Although many cell fates differ between males and females, probably the most ancient type of sexual dimorphism is the decision of germ cells to develop as sperm or as oocytes. Genetic analyses of Caenorhabditis elegans suggest that fog-3 might directly control this decision. We used transformation rescue to clone the fog-3 gene and show that it produces a single major transcript of approximately 1150 nucleotides. This transcript is predicted to encode a protein of 263 amino acids. One mutation causes a frame shift at the sixth codon and is thus likely to define the null phenotype of fog-3. Although the carboxyl-terminus of FOG-3 is novel, the amino-terminal domain is similar to that of the Tob, BTG1, and BTG2 proteins from vertebrates, which might suppress proliferation or promote differentiation. This domain is essential for FOG-3 activity, since six of eight missense mutations map to this region. Furthermore, this domain of BTG1 and BTG2 interacts with a transcriptional regulatory complex that has been conserved in all eukaryotes. Thus, one possibility is that FOG-3 controls transcription of genes required for germ cells to initiate spermatogenesis rather than oogenesis. This model implies that FOG-3 is required throughout an animal's life for germ cells to initiate spermatogenesis. We used RNA-mediated interference to demonstrate that fog-3 is indeed required continuously, which is consistent with this model.
Chen
P J
PJ
Department of Biology, University of Michigan, Ann Arbor, Michigan, 48109, USA.
Singal
A
A
Kimble
J
J
Ellis
R E
RE
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins; D003062:Codon; D003360:Cosmids; D004247:DNA; D018076:DNA, Complementary; D005260:Female; D016368:Frameshift Mutation; D005854:Germ Cells / Q000166:cytology*; D015801:Helminth Proteins / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D012727:Sex Characteristics; D013091:Spermatogenesis / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; D003062:Codon; D018076:DNA, Complementary; C403465:FOG-3 protein, C elegans; D015801:Helminth Proteins; D012333:RNA, Messenger; D004247:DNA