title: Meningeal retinoic acid contributes to neocortical lamination and radial migration during mouse brain development.
abstract: Retinoic acid (RA) is a diffusible molecule involved in early forebrain patterning. Its later production in the meninges by the retinaldehyde dehydrogenase RALDH2 coincides with the time of cortical neuron generation. A function of RA in this process has not been adressed directly asRaldh2-/-mouse mutants are embryonic lethal. Here, we used a conditional genetic strategy to inactivateRaldh2just prior to onset of its expression in the developing meninges. This inactivation does not affect the formation of the cortical progenitor populations, their rate of division, or timing of differentiation. However, migration of late-born cortical neurons is delayed, with neurons stalling in the intermediate zone and exhibiting an abnormal multipolar morphology. This suggests that RA controls the multipolar-to-bipolar transition that occurs in the intermediate zone and allows neurons to start locomotion in the cortical plate. Our work also shows a role for RA in cortical lamination, as deep layers are expanded and a subset of layer IV neurons are not formed in theRaldh2-ablated mutants. These data demonstrate that meninges are a source of extrinsic signals important for cortical development.
authors.affiliation: Development and Stem Cells Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch 67404, France.|Centre National de la Recherche Scientifique, UMR 7104, Illkirch 67404, France.|Institut National de la Santé et de la Recherche Médicale, U 964, Illkirch 67404, France.|Université de Strasbourg, Illkirch 67404, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Haushalter
authors.affiliation: Development and Stem Cells Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch 67404, France.|Centre National de la Recherche Scientifique, UMR 7104, Illkirch 67404, France.|Institut National de la Santé et de la Recherche Médicale, U 964, Illkirch 67404, France.|Université de Strasbourg, Illkirch 67404, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schuhbaur
authors.affiliation: Development and Stem Cells Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch 67404, France rhinn@igbmc.fr dolle@igbmc.fr.|Centre National de la Recherche Scientifique, UMR 7104, Illkirch 67404, France.|Institut National de la Santé et de la Recherche Médicale, U 964, Illkirch 67404, France.|Université de Strasbourg, Illkirch 67404, France.
authors.forename: Pascal
authors.identifier: http://orcid.org/0000-0002-9294-9090
authors.initials: P
authors.lastname: Dollé
authors.affiliation: Development and Stem Cells Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch 67404, France rhinn@igbmc.fr dolle@igbmc.fr.|Centre National de la Recherche Scientifique, UMR 7104, Illkirch 67404, France.|Institut National de la Santé et de la Recherche Médicale, U 964, Illkirch 67404, France.|Université de Strasbourg, Illkirch 67404, France.
authors.forename: Muriel
authors.identifier: http://orcid.org/0000-0002-1918-0246
authors.initials: M
authors.lastname: Rhinn
keywords: Cerebral cortex; Cortical layering; Neurons; Radial migration; Retinoids