@article{288c8a52fc41470bb0dea6357301ae43,
title = "FOXG1 Orchestrates Neocortical Organization and Cortico-Cortical Connections",
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]",
keywords = "BF1, Foxg1, Rp58, Zbtb18, Znf238, callosal projection, corpus callosum, cortex, development, radial migration, transcription factor",
author = "Francesca Cargnin and Kwon, {Ji Sun} and Sol Katzman and Bin Chen and Lee, {Jae W.} and Lee, {Soo Kyung}",
note = "Funding Information: We are grateful to Yuna Lee for the inspiration. The corpus callosum agenesis in her brain led to the diagnosis of the FOXG1 syndrome and inspired us to study the role of FOXG1 in corpus callosum formation. We are also thankful to Younjung Park for managing mouse colonies, generating antibodies, and excellent technical help; Gord Fishell and Goichi Miyoshi for Foxg1-floxed mice; Klaus-Armin Nave for NEX-Cre mice; Richard Maas for Robo mice; Paul Barnes and Kevin Wright for critical discussion and comments on the manuscript; and the Lee lab members for helpful discussion. This research was supported by grants from the NIH/NINDS ( R01NS054941 , R56NS054941 , and R01NS100471 to S.-K.L.; R01NS089777 to B.C.; and P30NS061800 to Neuroscience Imaging Center, OHSU), NIH/NIDDK ( R01DK064678 to J.W.L., and R01DK103661 to J.W.L. and S.-K.L.), NIH/NIMH ( R01MH094589 to B.C.), American Heart Association (to S.-K.L.), and Blackswan Foundation and FOXG1 Research Foundation (to J.W.L. and S.-K.L.). Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2018",
month = dec,
day = "5",
doi = "10.1016/j.neuron.2018.10.016",
language = "English (US)",
volume = "100",
pages = "1083--1096.e5",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "5",
}