Retinoic Acid from the Meninges Regulates Cortical Neuron Generation

Julie A. Siegenthaler, Amir M. Ashique, Konstantinos Zarbalis, Katelin P. Patterson, Jonathan H. Hecht, Maureen A. Kane, Alexandra E. Folias, Youngshik Choe, Scott R. May, Tsutomu Kume, Joseph L. Napoli, Andrew S. Peterson, Samuel J. Pleasure*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

281 Scopus citations


Extrinsic signals controlling generation of neocortical neurons during embryonic life have been difficult to identify. In this study we demonstrate that the dorsal forebrain meninges communicate with the adjacent radial glial endfeet and influence cortical development. We took advantage of Foxc1 mutant mice with defects in forebrain meningeal formation. Foxc1 dosage and loss of meninges correlated with a dramatic reduction in both neuron and intermediate progenitor production and elongation of the neuroepithelium. Several types of experiments demonstrate that retinoic acid (RA) is the key component of this secreted activity. In addition, Rdh10- and Raldh2-expressing cells in the dorsal meninges were either reduced or absent in the Foxc1 mutants, and Rdh10 mutants had a cortical phenotype similar to the Foxc1 null mutants. Lastly, in utero RA treatment rescued the cortical phenotype in Foxc1 mutants. These results establish RA as a potent, meningeal-derived cue required for successful corticogenesis.

Original languageEnglish (US)
Pages (from-to)597-609
Number of pages13
Issue number3
StatePublished - Oct 30 2009



ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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