Retinoic acid from the meninges regulates cortical neuron generation.
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.
Siegenthaler
Julie A
JA
Department of Neurology, Institute for Regenerative Medicine, University of California San Francisco, San Francisco, CA 94158, USA.
Ashique
Amir M
AM
Zarbalis
Konstantinos
K
Patterson
Katelin P
KP
Hecht
Jonathan H
JH
Kane
Maureen A
MA
Folias
Alexandra E
AE
Choe
Youngshik
Y
May
Scott R
SR
Kume
Tsutomu
T
Napoli
Joseph L
JL
Peterson
Andrew S
AS
Pleasure
Samuel J
SJ
D000818:Animals; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D008578:Meninges / Q000378:metabolism*; D051379:Mice; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology*; D016548:Prosencephalon / Q000166:cytology / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism*
D051858:Forkhead Transcription Factors; C112890:Foxc1 protein, mouse; D014212:Tretinoin