Dose-dependent control of proliferation and sperm specification by FOG-1/CPEB

Development. 2005 Aug;132(15):3471-81. doi: 10.1242/dev.01921. Epub 2005 Jul 6.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / physiology
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cell Division / physiology*
  • DNA Primers
  • Germ-Line Mutation
  • In Situ Hybridization
  • Male
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • RNA, Messenger / genetics
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / physiology
  • Sex Determination Processes
  • Spermatogenesis
  • Spermatozoa / classification
  • Spermatozoa / physiology*

Substances

  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • DNA Primers
  • Nuclear Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • fog-1 protein, C elegans