FOXG1 Orchestrates Neocortical Organization and Cortico-Cortical Connections

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2018 Nov 6

PMID 30392794

Citations 43

Authors

Francesca Cargnin

Ji-Sun Kwon

Sol Katzman

Bin Chen

Jae W Lee

Soo-Kyung Lee

Affiliations

Soon will be listed here.

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.

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