lin-35/Rb and the CoREST ortholog spr-1 coordinately regulate vulval morphogenesis and gonad development in C. elegans

Dev Biol. 2007 Feb 15;302(2):448-62. doi: 10.1016/j.ydbio.2006.09.051. Epub 2006 Oct 5.


Using a genetic screen to identify genes that carry out redundant functions during development with lin-35/Rb, the C. elegans Retinoblastoma family ortholog, we have identified a mutation in spr-1. spr-1 encodes the C. elegans ortholog of human CoREST, a protein containing Myb-like SANT and ELM2 domains, which functions as part of a transcriptional regulatory complex. CoREST recruits mediators of transcriptional repression, including histone deacetylase, and demethylase, and interacts with the tumor suppression protein REST. spr-1/CoREST was previously shown in C. elegans to suppress defects associated with loss of the presenilin sel-12, which functions in the proteolytic processing of LIN-12/Notch. Here we show that lin-35 and spr-1 coordinately regulate several developmental processes in C. elegans including the ingression of vulval cells as well as germline proliferation. We also show that loss of lin-35 and spr-1 hypersensitizes animals to a reduction in LIN-12/Notch activity, leading to the generation of proximal germline tumors. This defect, which is observed in lin-35; spr-1; lin-12(RNAi) and lin-35; spr-1; hop-1(RNAi) triple mutants is likely due to a delay in the entry of germ cells into meiosis.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / physiology*
  • Cell Proliferation
  • Chondroitin / biosynthesis
  • Female
  • Germ Cells / physiology
  • Gonads / growth & development
  • Gonads / physiology
  • Larva
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology
  • Models, Animal
  • Morphogenesis
  • Mutation
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Receptors, Notch / physiology
  • Repressor Proteins / genetics
  • Repressor Proteins / physiology*
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / physiology*
  • Signal Transduction
  • Vulva / growth & development
  • Vulva / physiology


  • Caenorhabditis elegans Proteins
  • Lin-12 protein, C elegans
  • Membrane Proteins
  • Receptors, Notch
  • Repressor Proteins
  • Retinoblastoma Protein
  • lin-35 protein, C elegans
  • Chondroitin