Olig bHLH proteins interact with homeodomain proteins to regulate cell fate acquisition in progenitors of the ventral neural tube

Curr Biol. 2001 Sep 18;11(18):1413-20. doi: 10.1016/s0960-9822(01)00441-9.

Abstract

Background: Organizing signals such as Sonic hedgehog are thought to specify neuronal subtype identity by regulating the expression of homeodomain proteins in progenitors of the embryonic neural tube. One of these, Nkx2.2, is necessary and sufficient for the development of V3 interneurons.

Results: We report that Olig genes, encoding basic helix-loop-helix (bHLH) proteins, are expressed in a subset of Nkx2.2 progenitors before the establishment of interneurons and oligodendroglial precursors. Gain-of-function analysis in transgenic mouse embryos indicates that Olig genes specifically inhibit the establishment of Sim1-expressing V3 interneurons. Moreover, coexpression of Olig2 with Nkx2.2 in the chick neural tube generated cells expressing Sox10, a marker of oligodendroglial precursors. Colocalization of Olig and Nkx2.2 proteins at the dorsal extent of the Nkx2.2 expression domain is consistent with regulatory interactions that define the potential of progenitor cells in the border region.

Conclusions: Interactions between homeodomain and Olig bHLH proteins evidently regulate neural cell fate acquisition and diversification in the ventral neural tube. In particular, interactions between Olig and Nkx2.2 proteins inhibit V3 interneuron development and promote the formation of alternate cell types, including those expressing Sox10.

Publication types

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

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Differentiation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression
  • Helix-Loop-Helix Motifs*
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Mice
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / cytology*
  • Neurons / metabolism
  • Oligodendrocyte Transcription Factor 2
  • SOXE Transcription Factors
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Zebrafish Proteins

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Nkx2.2 protein
  • Olig2 protein, mouse
  • Oligodendrocyte Transcription Factor 2
  • SOXE Transcription Factors
  • Sox10 protein, mouse
  • Transcription Factors
  • Zebrafish Proteins