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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 (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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Metadata
- 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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