Sonic hedgehog signaling regulates a novel epithelial progenitor domain of the hindbrain choroid plexus
Open accessAbstract
Choroid plexuses (ChPs) are vascularized secretory organs involved in the regulation of brain homeostasis, and function as the blood-cerebrospinal fluid (CSF) barrier. Despite their crucial roles, there is limited understanding of the regulatory mechanism driving ChP development. Sonic hedgehog (Shh), a secreted signal crucial for embryonic development and cancer, is strongly expressed in the differentiated hindbrain ChP epithelium (hChPe). However, we identify a distinct epithelial domain in the hChP that does not express Shh, but displays Shh signaling. We find that this distinct Shh target field that adjoins a germinal zone, the lower rhombic lip (LRL), functions as a progenitor domain by contributing directly to the hChPe. By conditional Shh mutant analysis, we show that Shh signaling regulates hChPe progenitor proliferation and hChPe expansion through late embryonic development, starting around E12.5. Whereas previous studies show that direct contribution to the hChPe by the LRL ceases around E14, our findings reveal a novel tissue-autonomous role for Shh production and signaling in driving the continual growth and expansion of the hindbrain choroid plexus throughout development.
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4V ChP fibroblasts expressed high levels of genes encoding signaling molecules with roles in hindbrain development.
“4V ChP fibroblasts also expressed high levels of genes encoding signaling molecules with roles in hindbrain development (e.g., Hhip (Chuang and McMahon, 1999), Ptch1 (Huang et al., 2009), Rbp4 (Chang et al., 2016), and Wisp1 (Lun et al., 2015a, Figure 4B, S4D).”
From A cellular and spatial map of the choroid plexus across brain ventricles and ages (2021) · cites this paper as Huang et al., 2009
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- Authors
- Huang, X., Ketova, T., Fleming, J. T., Wang, H., Dey, S. K., Litingtung, Y., & Chiang, C.
- Affiliations
- Vanderbilt University Medical Center (US)
- Chinese Academy of Sciences (CN)
- Cincinnati Children's Hospital Medical Center (US)
- Corresponding author
- Chiang, Chin
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2009-08-01
- Volume
- 136
- Issue
- 15
- Pages
- 2535-2543
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- PMC
- PMC2709062
- OpenAlex
- W2024357833
- Cited by
- 106
- References
- 35
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 8 · 2023: 7 · 2022: 8 · 2021: 7 · 2020: 5 · 2019: 8 · 2018: 6 · 2017: 1 · 2016: 3 · 2015: 9 · 2014: 6 · 2013: 7 · 2012: 7
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (T32CA119925)
- National Institute of Neurological Disorders and Stroke (NS042205, R01NS042205)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- Sonic hedgehog signaling, choroid plexus, progenitor cell proliferation, blood-CSF barrier, embryonic development
- MeSH terms
- Zinc Finger Protein GLI1, Animals, Animals, Newborn, Cell Differentiation, Choroid Plexus, Epithelial Cells, Models, Biological, Rhombencephalon, Stem Cells, Transcription Factors, Signal Transduction, Gene Deletion, Homeodomain Proteins, Integrases, Bone Morphogenetic Proteins, Cell Proliferation, Wnt Proteins, Mice, Kruppel-Like Transcription Factors, Hedgehog Proteins, Growth Differentiation Factors, LIM-Homeodomain Proteins
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