Retinoic acid from the meninges regulates cortical neuron generation.
Open accessAbstract
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.
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Production of RA by the arachnoid layers critically regulates brain and neurovascular development.
“Production of RA by the arachnoid layers critically regulates brain and neurovascular development (Siegenthaler et al., 2009; Choi et al., 2014; Bonney et al., 2016; Mishra et al., 2016; Haushalter et al., 2017).”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as Siegenthaler et al., 2009
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Self-citationInflammation of the Embryonic Choroid Plexus Barrier following Maternal Immune Activation
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‘Sealing off the CNS’: cellular and molecular regulation of blood–brain barriergenesis
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Analysis, occurrence, and function of 9-cis-retinoic acid
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B-1a lymphocytes promote oligodendrogenesis during brain development
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Outer brain barriers in rat and human development
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Cortical Gyrification Induced by Fibroblast Growth Factor 2 in the Mouse Brain
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Cortical neurogenesis and morphogens: diversity of cues, sources and functions
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Neural Progenitor Cell Polarity and Cortical Development
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TAG-1–assisted progenitor elongation streamlines nuclear migration to optimize subapical crowding
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Forkhead box transcription factor FoxC1 preserves corneal transparency by regulating vascular growth
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Self-citationThe path from the choroid plexus to the subventricular zone: go with the flow!
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Control of asymmetric cell division of mammalian neural progenitors
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Neural Stem Cell Niches in Health and Diseases
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A Cascade of Morphogenic Signaling Initiated by the Meninges Controls Corpus Callosum Formation
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Self-citationRetinoic Acid Functions as a Key GABAergic Differentiation Signal in the Basal Ganglia
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Shaping the brain: The emergence of cortical structure and folding
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Self-citationIGF-II Promotes Stemness of Neural Restricted Precursors
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Patterning the cerebral cortex: traveling with morphogens
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Thyroid hormone availability in the human fetal brain: novel entry pathways and role of radial glia
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Foxc1 is required by pericytes during fetal brain angiogenesis
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- Authors
- Siegenthaler, J. A., Ashique, A. M., Zarbalis, K., Patterson, K. P., Hecht, J. H., Kane, M. A., Folias, A. E., Choe, Y., May, S. R., Kume, T., Napoli, J. L., Peterson, A. S., & Pleasure, S. J.
- Affiliations
- University of California, San Francisco (US)
- Genentech (US)
- University of California, Berkeley (US)
- Salk Institute for Biological Studies (US)
- Vanderbilt University Medical Center (US)
- Corresponding author
- Pleasure, Samuel J.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 139
- Issue
- 3
- Pages
- 597-609
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC2772834
- OpenAlex
- W2083131697
- Cited by
- 402
- References
- 51
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 17 · 2023: 21 · 2022: 28 · 2021: 17 · 2020: 26 · 2019: 27 · 2018: 20 · 2017: 33 · 2016: 25 · 2015: 24 · 2014: 29 · 2013: 37 · 2012: 34
- FWCI
- 8.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1385 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Autism Speaks (AS1625)
- National Institute of Mental Health (K02MH074958)
- National Institute on Drug Abuse (R56DA017627, R01DA017627)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- retinoic acid, meninges, cortical development, FOXC1, intermediate progenitor cells, RDH10, Raldh2, dorsal forebrain
- MeSH terms
- Animals, Meninges, Neurons, Tretinoin, Prosencephalon, Mice, Forkhead Transcription Factors, Neurogenesis, In Vitro Techniques
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