Pbx Regulates Patterning of the Cerebral Cortex in Progenitors and Postmitotic Neurons

Neuron. 2015 Dec 16;88(6):1192-1207. doi: 10.1016/j.neuron.2015.10.045. Epub 2015 Dec 6.

Abstract

We demonstrate using conditional mutagenesis that Pbx1, with and without Pbx2(+/-) sensitization, regulates regional identity and laminar patterning of the developing mouse neocortex in cortical progenitors (Emx1-Cre) and in newly generated neurons (Nex1-Cre). Pbx1/2 mutants have three salient molecular phenotypes of cortical regional and laminar organization: hypoplasia of the frontal cortex, ventral expansion of the dorsomedial cortex, and ventral expansion of Reelin expression in the cortical plate of the frontal cortex, concomitant with an inversion of cortical layering in the rostral cortex. Molecular analyses, including PBX ChIP-seq, provide evidence that PBX promotes frontal cortex identity by repressing genes that promote dorsocaudal fate.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Cerebral Cortex / embryology*
  • Cerebral Cortex / growth & development*
  • Homeodomain Proteins / physiology*
  • Mice
  • Mice, Transgenic
  • Mitosis / physiology
  • Neural Stem Cells / physiology*
  • Neurons / physiology*
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Reelin Protein
  • Stem Cells / physiology
  • Transcription Factors / physiology*

Substances

  • Homeodomain Proteins
  • Pbx1 protein, mouse
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Reelin Protein
  • Transcription Factors
  • RELN protein, human
  • Reln protein, mouse

Associated data

  • GEO/GSE73288