Dose-dependent control of proliferation and sperm specification by FOG-1/CPEB.
RNA-binding proteins control germline development in metazoans. This work focuses on control of the C. elegans germline by two RNA-binding proteins: FOG-1, a CPEB homolog; and FBF, a PUF family member. Previous studies have shown that FOG-1 specifies the sperm fate and that FBF promotes proliferation. Here, we report that FOG-1 also promotes proliferation. Whereas fbf-1 fbf-2 double mutants make approximately 120 germ cells, fog-1; fbf-1 fbf-2 triple mutants make only approximately 10 germ cells. The triple mutant germline divides normally until early L2, when germ cells prematurely enter meiosis and begin oogenesis. Importantly, fog-1/+; fbf-1 fbf-2 animals make more germ cells than fbf-1 fbf-2 double mutants, demonstrating that one dose of wild-type fog-1 promotes proliferation more effectively than two doses - at least in the absence of FBF. FOG-1 protein is barely detectable in proliferating germ cells, but abundant in germ cells destined for spermatogenesis. Based on fog-1 dose effects, together with the gradient of FOG-1 protein abundance, we suggest that low FOG-1 promotes proliferation and high FOG-1 specifies spermatogenesis. FBF binds specifically to regulatory elements in the fog-1 3'UTR, and FOG-1 increases in animals lacking FBF. Therefore, FBF represses fog-1 expression. We suggest that FBF promotes continued proliferation, at least in part, by maintaining FOG-1 at a low level appropriate for proliferation. The dose-dependent control of proliferation and cell fate by FOG-1 has striking parallels with Xenopus CPEB, suggesting a conserved mechanism in animal development.
Thompson
Beth E
BE
Cellular and Molecular Biology Training Program, University of Wisconsin-Madison, Madison, WI 53706, USA.
Bernstein
David S
DS
Bachorik
Jennifer L
JL
Petcherski
Andrei G
AG
Wickens
Marvin
M
Kimble
Judith
J
D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D017931:DNA Primers; D018095:Germ-Line Mutation; D017403:In Situ Hybridization; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D019849:Sex Determination Processes; D013091:Spermatogenesis; D013094:Spermatozoa / Q000145:classification / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D017931:DNA Primers; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C498431:fog-1 protein, C elegans