FOXG1 Orchestrates Neocortical Organization and Cortico-Cortical Connections

Francesca Cargnin, Ji Sun Kwon, Sol Katzman, Bin Chen, Jae Lee, Soo-Kyung Lee

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The hallmarks of FOXG1 syndrome, which results from mutations in a single FOXG1 allele, include cortical atrophy and corpus callosum agenesis. However, the etiology for these structural deficits and the role of FOXG1 in cortical projection neurons remain unclear. Here we demonstrate that Foxg1 in pyramidal neurons plays essential roles in establishing cortical layers and the identity and axon trajectory of callosal projection neurons. The neuron-specific actions of Foxg1 are achieved by forming a transcription complex with Rp58. The Foxg1-Rp58 complex directly binds and represses Robo1, Slit3, and Reelin genes, the key regulators of callosal axon guidance and neuronal migration. We also found that inactivation of one Foxg1 allele specifically in cortical neurons was sufficient to cause cerebral cortical hypoplasia and corpus callosum agenesis. Together, this study reveals a novel gene regulatory pathway that specifies neuronal characteristics during cerebral cortex development and sheds light on the etiology of FOXG1 syndrome. Video Abstract: [Figure presented]

Original languageEnglish (US)
Pages (from-to)1083-1096.e5
JournalNeuron
Volume100
Issue number5
DOIs
StatePublished - Dec 5 2018

Fingerprint

Agenesis of Corpus Callosum
Neurons
Corpus Callosum
Regulator Genes
Alleles
Pyramidal Cells
Cerebral Cortex
Atrophy
Axons
Mutation
Axon Guidance

Keywords

  • BF1
  • callosal projection
  • corpus callosum
  • cortex
  • development
  • Foxg1
  • radial migration
  • Rp58
  • transcription factor
  • Zbtb18
  • Znf238

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

FOXG1 Orchestrates Neocortical Organization and Cortico-Cortical Connections. / Cargnin, Francesca; Kwon, Ji Sun; Katzman, Sol; Chen, Bin; Lee, Jae; Lee, Soo-Kyung.

In: Neuron, Vol. 100, No. 5, 05.12.2018, p. 1083-1096.e5.

Research output: Contribution to journalArticle

Cargnin, Francesca ; Kwon, Ji Sun ; Katzman, Sol ; Chen, Bin ; Lee, Jae ; Lee, Soo-Kyung. / FOXG1 Orchestrates Neocortical Organization and Cortico-Cortical Connections. In: Neuron. 2018 ; Vol. 100, No. 5. pp. 1083-1096.e5.
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