+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Meningeal retinoic acid contributes to neocortical lamination and radial migration during mouse brain development

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          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 as Raldh2 −/− mouse mutants are embryonic lethal. Here, we used a conditional genetic strategy to inactivate Raldh2 just 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 the Raldh2-ablated mutants. These data demonstrate that meninges are a source of extrinsic signals important for cortical development.


          Summary: Involvement of the signalling molecule retinoic acid in neurogenesis of the developing cerebral cortex is shown through targeted deletion of its synthesizing enzyme.

          Related collections

          Most cited references 63

          • Record: found
          • Abstract: not found
          • Article: not found

          The cell biology of neurogenesis.

          During the development of the mammalian central nervous system, neural stem cells and their derivative progenitor cells generate neurons by asymmetric and symmetric divisions. The proliferation versus differentiation of these cells and the type of division are closely linked to their epithelial characteristics, notably, their apical-basal polarity and cell-cycle length. Here, we discuss how these features change during development from neuroepithelial to radial glial cells, and how this transition affects cell fate and neurogenesis.
            • Record: found
            • Abstract: found
            • Article: not found

            Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases.

            Precise patterns of cell division and migration are crucial to transform the neuroepithelium of the embryonic forebrain into the adult cerebral cortex. Using time-lapse imaging of clonal cells in rat cortex over several generations, we show here that neurons are generated in two proliferative zones by distinct patterns of division. Neurons arise directly from radial glial cells in the ventricular zone (VZ) and indirectly from intermediate progenitor cells in the subventricular zone (SVZ). Furthermore, newborn neurons do not migrate directly to the cortex; instead, most exhibit four distinct phases of migration, including a phase of retrograde movement toward the ventricle before migration to the cortical plate. These findings provide a comprehensive and new view of the dynamics of cortical neurogenesis and migration.
              • Record: found
              • Abstract: found
              • Article: not found

              Neuronal subtype specification in the cerebral cortex.

              In recent years, tremendous progress has been made in understanding the mechanisms underlying the specification of projection neurons within the mammalian neocortex. New experimental approaches have made it possible to identify progenitors and study the lineage relationships of different neocortical projection neurons. An expanding set of genes with layer and neuronal subtype specificity have been identified within the neocortex, and their function during projection neuron development is starting to be elucidated. Here, we assess recent data regarding the nature of neocortical progenitors, review the roles of individual genes in projection neuron specification and discuss the implications for progenitor plasticity.

                Author and article information

                Biol Open
                Biol Open
                Biology Open
                The Company of Biologists Ltd
                15 February 2017
                23 December 2016
                23 December 2016
                : 6
                : 2
                : 148-160
                [1 ]Development and Stem Cells Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire , Illkirch 67404, France
                [2 ]Centre National de la Recherche Scientifique, UMR 7104 , Illkirch 67404, France
                [3 ]Institut National de la Santé et de la Recherche Médicale, U 964 , Illkirch 67404, France
                [4 ]Université de Strasbourg , Illkirch 67404, France
                Author notes
                [* ]Authors for correspondence ( rhinn@ ; dolle@ )
                © 2017. Published by The Company of Biologists Ltd

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                Funded by: Agence Nationale de la Recherche,;
                Award ID: ANR-11-BSV2-0003
                Award ID: ANR-10-LABX-0030-INRT
                Award ID: ANR-10-IDEX-0002-02
                Funded by: Hôpitaux Universitaires de Strasbourg;
                Funded by: Institut National de la Santé et de la Recherche Médicale,;
                Funded by: Association pour la Recherche sur le Cancer,;
                Research Article

                Life sciences

                cortical layering, radial migration, neurons, cerebral cortex, retinoids


                Comment on this article