Cited2 regulates neocortical layer II/III generation and somatosensory callosal projection neuron development and connectivity

Ryann M. Fame, Jessica MacDonald, Sally L. Dunwoodie, Emi Takahashi, Jeffrey D. Macklis

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

The neocortex contains hundreds to thousands of distinct subtypes of precisely connected neurons, allowing it to perform remarkably complex tasks of high-level cognition. Callosal projection neurons (CPN) connect the cerebral hemispheres via the corpus callosum, integrating cortical information and playing key roles in associative cognition. CPN are a strikingly diverse set of neuronal subpopulations, and development of this diversity requires precise control by a complex, interactive set of molecular effectors. We have found that the transcriptional coregulator Cited2 regulates and refines two stages of CPN development. Cited2 is expressed broadly by progenitors in the embryonic day 15.5 subventricular zone, during the peak of superficial layer CPN birth, with a progressive postmitotic refinement in expression, becoming restricted to CPN of the somatosensory cortex postnatally. We generated progenitor-stage and postmitotic forebrain-specific Cited2 conditional knock-out mice, using the Emx1-Cre and NEX-Cre mouse lines, respectively. We demonstrate that Cited2 functions in progenitors, but is not necessary postmitotically, to regulate both (1) broad generation of layer II/III CPN and (2) acquisition of precise area-specific molecular identity and axonal/dendritic connectivity of somatosensory CPN. This novel CPN subtype-specific and area-specific control from progenitor action of Cited2 adds yet another layer of complexity to the multistage developmental regulation of neocortical development.

Original languageEnglish (US)
Pages (from-to)6403-6419
Number of pages17
JournalJournal of Neuroscience
Volume36
Issue number24
DOIs
StatePublished - Jun 15 2016

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Keywords

  • Arealization
  • Callosum
  • Neocortex
  • Neuronal differentiation
  • Somatosensory

ASJC Scopus subject areas

  • Neuroscience(all)

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