Ventral neural patterning by Nkx homeobox genes: Nkx6.1 controls somatic motor neuron and ventral interneuron fates

Genes Dev. 2000 Sep 1;14(17):2134-9. doi: 10.1101/gad.820400.

Abstract

There is growing evidence that sonic hedgehog (Shh) signaling regulates ventral neuronal fate in the vertebrate central nervous system through Nkx-class homeodomain proteins. We have examined the patterns of neurogenesis in mice carrying a targeted mutation in Nkx6.1. These mutants show a dorsal-to-ventral switch in the identity of progenitors and in the fate of postmitotic neurons. At many axial levels there is a complete block in the generation of V2 interneurons and motor neurons and a compensatory ventral expansion in the domain of generation of V1 neurons, demonstrating the essential functions of Nkx6.1 in regional patterning and neuronal fate determination.

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 Lineage
  • Cells, Cultured
  • DNA-Binding Proteins / biosynthesis
  • Gene Targeting
  • Hedgehog Proteins
  • Homeodomain Proteins / biosynthesis
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / physiology*
  • Immunohistochemistry
  • In Situ Hybridization
  • LIM-Homeodomain Proteins
  • Mice
  • Motor Neurons / metabolism*
  • Mutagenesis, Site-Directed
  • Nerve Tissue Proteins*
  • PAX2 Transcription Factor
  • Protein Biosynthesis
  • Repressor Proteins / biosynthesis
  • Signal Transduction
  • Spinal Cord / embryology
  • Stem Cells / metabolism
  • Time Factors
  • Tissue Distribution
  • Trans-Activators*
  • Transcription Factors / biosynthesis

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Hedgehog Proteins
  • Homeodomain Proteins
  • ISL2 protein, human
  • Isl-2 protein, vertebrate
  • Isl2 protein, mouse
  • LIM-Homeodomain Proteins
  • Lhx3 protein
  • Nerve Tissue Proteins
  • Nkx6-1 protein, mouse
  • PAX2 Transcription Factor
  • Pax2 protein, mouse
  • Repressor Proteins
  • SHH protein, human
  • SIM1 protein, human
  • Sim1 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • VSX2 protein, human
  • Vsx2 protein, mouse
  • insulin gene enhancer binding protein Isl-1