Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications

Elife. 2016 Jan 27;5:e09531. doi: 10.7554/eLife.09531.

Abstract

During cortical development, the identity of major classes of long-distance projection neurons is established by the expression of molecular determinants, which become gradually restricted and mutually exclusive. However, the mechanisms by which projection neurons acquire their final properties during postnatal stages are still poorly understood. In this study, we show that the number of neurons co-expressing Ctip2 and Satb2, respectively involved in the early specification of subcerebral and callosal projection neurons, progressively increases after birth in the somatosensory cortex. Ctip2/Satb2 postnatal co-localization defines two distinct neuronal subclasses projecting either to the contralateral cortex or to the brainstem suggesting that Ctip2/Satb2 co-expression may refine their properties rather than determine their identity. Gain- and loss-of-function approaches reveal that the transcriptional adaptor Lmo4 drives this maturation program through modulation of epigenetic mechanisms in a time- and area-specific manner, thereby indicating that a previously unknown genetic program postnatally promotes the acquisition of final subtype-specific features.

Keywords: Ctip2/Satb2 coexpression; Lmo4; cerebral cortex; developmental biology; epigenetic mechanism; layer V projection neurons; mouse; neuroscience; postnatal differentiation; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Epigenesis, Genetic*
  • Gene Expression Regulation, Developmental
  • LIM Domain Proteins / metabolism
  • Matrix Attachment Region Binding Proteins / analysis
  • Mice
  • Neurons / physiology*
  • Repressor Proteins / analysis
  • Somatosensory Cortex / embryology*
  • Transcription Factors / analysis
  • Tumor Suppressor Proteins / analysis

Substances

  • Adaptor Proteins, Signal Transducing
  • Bcl11b protein, mouse
  • LIM Domain Proteins
  • Lmo4 protein, mouse
  • Matrix Attachment Region Binding Proteins
  • Repressor Proteins
  • SATB2 protein, mouse
  • Transcription Factors
  • Tumor Suppressor Proteins

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.