期刊
BIOLOGY OPEN
卷 6, 期 2, 页码 148-160出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/bio.021063
关键词
Retinoids; Cerebral cortex; Neurons; Radial migration; Cortical layering
类别
资金
- Agence Nationale de la Recherche (ANR) [ANR-11-BSV2-0003]
- Labx [ANR-10-LABX-0030-INRT, ANR-10-IDEX-0002-02]
- Hopitaux Universitaires de Strasbourg
- Institut National de la Sante et de la Recherche Medicale, Region Alsace
- Association pour la Recherche sur le Cancer (ARC)
- Agence Nationale de la Recherche (ANR) [ANR-11-BSV2-0003] Funding Source: Agence Nationale de la Recherche (ANR)
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.
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