Ctip1 Controls Acquisition of Sensory Area Identity and Establishment of Sensory Input Fields in the Developing Neocortex

Neuron. 2016 Apr 20;90(2):261-77. doi: 10.1016/j.neuron.2016.03.008.

Abstract

While transcriptional controls over the size and relative position of cortical areas have been identified, less is known about regulators that direct acquisition of area-specific characteristics. Here, we report that the transcription factor Ctip1 functions in primary sensory areas to repress motor and activate sensory programs of gene expression, enabling establishment of sharp molecular boundaries defining functional areas. In Ctip1 mutants, abnormal gene expression leads to aberrantly motorized corticocortical and corticofugal output connectivity. Ctip1 critically regulates differentiation of layer IV neurons, and selective loss of Ctip1 in cortex deprives thalamocortical axons of their receptive "sensory field" in layer IV, which normally provides a tangentially and radially defined compartment of dedicated synaptic territory. Therefore, although thalamocortical axons invade appropriate cortical regions, they are unable to organize into properly configured sensory maps. Together, these data identify Ctip1 as a critical control over sensory area development.

MeSH terms

  • Animals
  • Axons / physiology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Cell Differentiation / genetics
  • DNA-Binding Proteins
  • Gene Expression Regulation, Developmental / genetics
  • Mice
  • Mice, Knockout
  • Mutation
  • Neocortex / cytology
  • Neocortex / growth & development*
  • Neocortex / physiology*
  • Neurons / physiology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology*
  • Repressor Proteins
  • Signal Transduction / physiology
  • Thalamus / cytology
  • Thalamus / physiology*

Substances

  • Bcl11a protein, mouse
  • Carrier Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Repressor Proteins