A mutation in teg-4, which encodes a protein homologous to the SAP130 pre-mRNA splicing factor, disrupts the balance between proliferation and differentiation in the C. elegans germ line

Mech Dev. May-Jun 2009;126(5-6):417-29. doi: 10.1016/j.mod.2009.01.006. Epub 2009 Feb 1.

Abstract

Dividing stem cells can give rise to two types of daughter cells; self-renewing cells that have virtually the same properties as the parent cell, and differentiating cells that will eventually form part of a tissue. The Caenorhabditis elegans germ line serves as a model to study how the balance between these two types of daughter cells is maintained. A mutation in teg-4 causes over-proliferation of the stem cells, thereby disrupting the balance between proliferation and differentiation. We have cloned teg-4 and found it to encode a protein homologous to the highly conserved splicing factor subunit 3 of SF3b. Our allele of teg-4 partially reduces TEG-4 function. In an effort to determine how teg-4 functions in controlling stem cell proliferation, we have performed genetic epistasis analysis with known factors controlling stem cell proliferation. We found that teg-4 is synthetic tumorous with genes in both major redundant genetic pathways that function downstream of GLP-1/Notch signaling to control the balance between proliferation and differentiation. Therefore, teg-4 is unlikely to function specifically in either of these two genetic pathways. Further, the synthetic tumorous phenotype seen with one of the genes from these pathways is epistatic to glp-1, indicating that teg-4 functions downstream of glp-1, likely as a positive regulator of meiotic entry. We propose that a reduction in teg-4 activity reduces the splicing efficiency of targets involved in controlling the balance between proliferation and differentiation. This results in a shift in the balance towards proliferation, eventually forming a germline tumor.

Publication types

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

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / chemistry
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Differentiation*
  • Cell Proliferation
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / metabolism
  • Epistasis, Genetic
  • Germ Cells / cytology*
  • Germ Cells / metabolism
  • Larva / growth & development
  • Membrane Glycoproteins / metabolism
  • Molecular Sequence Data
  • Mutation / genetics*
  • Phenotype
  • Protein Subunits / metabolism
  • RNA Precursors / genetics*
  • RNA-Binding Proteins / chemistry*
  • Receptors, Notch / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Temperature

Substances

  • Caenorhabditis elegans Proteins
  • Glp-1 protein, C elegans
  • Membrane Glycoproteins
  • Protein Subunits
  • RNA Precursors
  • RNA-Binding Proteins
  • Receptors, Notch