The C. elegans glycopeptide hormone receptor ortholog, FSHR-1, regulates germline differentiation and survival.
BACKGROUND
The mammalian glycopeptide hormone receptors (GPHRs) are key regulators of reproductive development, and their homologs are widely distributed throughout the animal kingdom. The C. elegans genome encodes a single GPHR family member, FSHR-1, which shares equal identity to the FSH, LH, and TSH receptors from mammals.


RESULTS
Because loss of fshr-1 function does not produce a visible phenotype in C. elegans, we conducted a genome-wide RNAi-feeding screen to identify genes that perform functions that overlap with those of fshr-1. This approach led to the identification of the PUF family members fbf-1 and fbf-2 (the fbfs). Whereas a weak reduction in fbf activity caused little or no discernable effect in the wild-type, an equivalent loss in the fshr-1(0) mutant background resulted in a highly penetrant germline-masculinization phenotype. Furthermore, many fshr-1(0);fbf(RNAi) animals failed to maintain a germline stem cell niche. We also show that fshr-1 and the fbfs promote germline survival and prevent apoptosis with fog-1 and fog-3 and that simultaneous loss of fshr-1 and the fbfs can override the canonical requirement for fog-1 and fog-3 in the execution of the male-germline fate. Finally, we provide evidence that FSHR-1 controls germline processes nonautonomously via the soma and that FSHR-1 acts through a canonical signaling pathway involving Galpha(s) and adenyl cyclase.


CONCLUSIONS
Our results indicate a conserved role for GPHR family receptors in controlling germline development and fertility. Our data suggest a model whereby FSHR-1 signaling acts in parallel to the known sex-determination pathway to control multiple aspects of germline development.
Cho
Saeyoull
S
University of Wyoming, College of Agriculture, Department of Molecular Biology, Department 3944, 1000 E. University Avenue, Laramie, Wyoming 82071, USA.
Rogers
Katherine W
KW
Fay
David S
DS
D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D002470:Cell Survival; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D005854:Germ Cells / Q000166:cytology*; D008297:Male; D009866:Oogenesis; D016601:RNA-Binding Proteins / Q000378:metabolism; D011962:Receptors, FSH / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology
D029742:Caenorhabditis elegans Proteins; C403465:FOG-3 protein, C elegans; D016601:RNA-Binding Proteins; D011962:Receptors, FSH; C109286:fem-3-binding protein, C elegans; C498431:fog-1 protein, C elegans; D019204:GTP-Binding Proteins