Different Levels of Repressor Activity Assign Redundant and Specific Roles to Nkx6 Genes in Motor Neuron and Interneuron Specification

Neuron. 2001 Sep 13;31(5):743-55. doi: 10.1016/s0896-6273(01)00412-3.

Abstract

Specification of neuronal fate in the vertebrate central nervous system depends on the profile of transcription factor expression by neural progenitor cells, but the precise roles of such factors in neurogenesis remain poorly characterized. Two closely related transcriptional repressors, Nkx6.2 and Nkx6.1, are expressed by progenitors in overlapping domains of the ventral spinal cord. We provide genetic evidence that differences in the level of repressor activity of these homeodomain proteins underlies the diversification of interneuron subtypes, and provides a fail-safe mechanism during motor neuron generation. A reduction in Nkx6 activity further permits V0 neurons to be generated from progenitors that lack homeodomain proteins normally required for their generation, providing direct evidence for a model in which progenitor homeodomain proteins direct specific cell fates by actively suppressing the expression of transcription factors that direct alternative fates.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Lineage / physiology
  • Central Nervous System / cytology
  • Central Nervous System / embryology*
  • Central Nervous System / metabolism
  • Chick Embryo
  • Eye Proteins
  • Fetus
  • Gene Expression Regulation, Developmental / physiology
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Immunohistochemistry
  • In Situ Hybridization
  • Interneurons / cytology*
  • Interneurons / metabolism
  • Mice
  • Mice, Knockout / embryology
  • Mice, Knockout / genetics
  • Mice, Knockout / metabolism
  • Motor Neurons / cytology*
  • Motor Neurons / metabolism
  • PAX6 Transcription Factor
  • PAX7 Transcription Factor
  • Paired Box Transcription Factors
  • Repressor Proteins / genetics*
  • Spinal Cord / cytology
  • Spinal Cord / embryology
  • Spinal Cord / metabolism
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Transcription Factors / genetics*
  • Transcription, Genetic / physiology
  • Zebrafish Proteins

Substances

  • Dbx1 protein, mouse
  • Dbx2 protein, mouse
  • Eye Proteins
  • Homeodomain Proteins
  • Nkx2.2 protein
  • Nkx6-1 protein, mouse
  • Nkx6.2 protein, vertebrate
  • PAX6 Transcription Factor
  • PAX7 Transcription Factor
  • Paired Box Transcription Factors
  • Pax6 protein, mouse
  • Pax7 protein, mouse
  • Repressor Proteins
  • Transcription Factors
  • Zebrafish Proteins