A Novel Member of the Tob Family of Proteins Controls Sexual Fate in Caenorhabditis elegans Germ Cells

Abstract

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.

BTG2 antiproliferative protein interacts with the human CCR4 complex existing in vivo in three cell-cycle-regulated forms

“…All described components of human CCR4-NOT complexes have yeast orthologs, indicating that the biological functions of these complexes are conserved through eukaryotic evolution. In contrast, proteins homologous to BTG/TOB have been detected in all animals (Chen et al, 2000) but not in the yeast S. cerevisiae. The presence of BTG2 in CCR4-NOT complexes might thus indicate the metazoan evolution of regulatory or signal domains of signal transduction.…”

Identification of functional domains involved in BTG1 cell localization

“…Besides the general antiproliferative activity of this family, Xbtg1 has been implicated in gastrulation movements, and is a target of Xbra and Pintallavis, two genes playing a major role in the early events of Xenopus development (Saka et al, 2000). In addition, a novel member of the family, FOG3, controls sexual fate in Caenorhabditis elegans germ cells (Chen et al, 2000). Moreover, it has also been reported that TIS 21 expression identi®es single neuroepithelial cells that switch from proliferative to neuron-generating divisions (Iacopetti et al, 1999).…”

Genetics of germ cell development

“…FOG-1, a cytoplasmic poly-A element binding (CPEB) protein, and FOG-3, a Tob/BTG transcriptional/translational regulator, promote SPERMATOGENESIS; they are inhibited by the FBF proteins and by TRA-1, a conserved transcription factor that promotes female/hermaphrodite specification in somatic tissues (reviewed in refs 62 and 63). [62][63][64][65][66][67][68] TRA-1 is inhibited by FEM-3, which acts along with the additional factors FEM-1 and FEM-2 to push the germ cells toward continued spermatogenesis. 69,70 FEM-3 is opposed by the RNA-binding protein DAZ-1, which promotes the switch to OOGENESIS.…”