Bhlhb5 regulates the postmitotic acquisition of area identities in layers II-V of the developing neocortex

Neuron. 2008 Oct 23;60(2):258-72. doi: 10.1016/j.neuron.2008.08.006.

Abstract

While progenitor-restricted factors broadly specify area identities in developing neocortex, the downstream regulatory elements involved in acquisition of those identities in postmitotic neurons are largely unknown. Here, we identify Bhlhb5, a transcription factor expressed in layers II-V, as a postmitotic regulator of area identity. Bhlhb5 is initially expressed in a high caudomedial to low rostrolateral gradient that transforms into a sharp border between sensory and rostral motor cortices. Bhlhb5 null mice exhibit aberrant expression of area-specific genes and structural organization in the somatosensory and caudal motor cortices. In somatosensory cortex, Bhlhb5 null mice display postsynaptic disorganization of vibrissal barrels. In caudal motor cortex, Bhlhb5 null mice exhibit anomalous differentiation of corticospinal motor neurons, accompanied by failure of corticospinal tract formation. Together, these results demonstrate Bhlhb5's function as an area-specific transcription factor that regulates the postmitotic acquisition of area identities and elucidate the genetic hierarchy between progenitors and postmitotic neurons driving neocortical arealization.

Publication types

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

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Body Patterning / genetics
  • Cell Differentiation / genetics
  • Cell Movement / genetics
  • Efferent Pathways / cytology
  • Efferent Pathways / embryology
  • Efferent Pathways / metabolism
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Mitosis / genetics
  • Motor Cortex / cytology
  • Motor Cortex / embryology
  • Motor Cortex / metabolism
  • Neocortex / cytology
  • Neocortex / embryology*
  • Neocortex / metabolism*
  • Neurons / cytology
  • Neurons / metabolism*
  • Pyramidal Tracts / cytology
  • Pyramidal Tracts / embryology
  • Pyramidal Tracts / metabolism
  • Somatosensory Cortex / cytology
  • Somatosensory Cortex / embryology
  • Somatosensory Cortex / metabolism
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Telencephalon / cytology
  • Telencephalon / embryology
  • Telencephalon / metabolism
  • Transcriptional Activation / genetics

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Bhlhe22 protein, mouse