WNT5A is transported via lipoprotein particles in the cerebrospinal fluid to regulate hindbrain morphogenesis
Open accessAbstract
WNTs are lipid-modified proteins that control multiple functions in development and disease via short- and long-range signaling. However, it is unclear how these hydrophobic molecules spread over long distances in the mammalian brain. Here we show that WNT5A is produced by the choroid plexus (ChP) of the developing hindbrain, but not the telencephalon, in both mouse and human. Since the ChP produces and secretes the cerebrospinal fluid (CSF), we examine the presence of WNT5A in the CSF and find that it is associated with lipoprotein particles rather than exosomes. Moreover, since the CSF flows along the apical surface of hindbrain progenitors not expressing Wnt5a, we examined whether deletion of Wnt5a in the ChP controls their function and find that cerebellar morphogenesis is impaired. Our study thus identifies the CSF as a route and lipoprotein particles as a vehicle for long-range transport of biologically active WNT in the central nervous system.
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Wnt5a was most robustly expressed by mesenchymal cells and its receptor Ror1 was expressed, amongst others, by epithelial cells, suggesting lifelong contributions to ChP function.
“Wnt5a, a regulator of 4V ChP and hindbrain development (Kaiser et al., 2019), was most robustly expressed by mesenchymal cells and its receptor Ror1 was expressed, amongst others, by epithelial cells, suggesting lifelong contributions to ChP function (Figure S7C).”
From A cellular and spatial map of the choroid plexus across brain ventricles and ages (2021) · cites this paper as Kaiser et al., 2019
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A cellular and spatial map of the choroid plexus across brain ventricles and ages
Dani, N., Herbst, R. H., McCabe, C., Green, G. S., Kaiser, K., Head, J. P., Cui, J., Shipley, F. B., Jang, A., Dionne, D., et al. (2021) · Cell · doi:10.1016/j.cell.2021.04.003 · Cited by 388 · see citing works
Self-citation
- Authors
- Kaiser, K., Gyllborg, D., Procházka, J., Salašová, A., Kompaníková, P., Molina, F. L., Laguna-Goya, R., Radaszkiewicz, T., Harnoš, J., Procházková, M., Potěšil, D., Barker, R. A., Casado, Á. G., Zdráhal, Z., Sedláček, R., Arenas, E., Villaescusa, J. C., & Bryja, V.
- Affiliations
- Masaryk University (CZ)
- Karolinska Institutet (SE)
- Czech Academy of Sciences, Institute of Molecular Genetics (CZ)
- Aarhus University (DK)
- Central European Institute of Technology (CZ)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- Karolinska University Hospital (SE)
- Corresponding author
- Arenas, Ernest
- Villaescusa, J. Carlos
- ORCID
- Venue
- Nature Communications
- Published
- 2019-04-02
- Volume
- 10
- Issue
- 1
- Pages
- 1498-1498
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6445127
- OpenAlex
- W2932576377
- Cited by
- 87
- References
- 63
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 13 · 2023: 14 · 2022: 9 · 2021: 15 · 2020: 16 · 2019: 8
- FWCI
- 3.97
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UVaDOC UVaDOC University of Valladolid Documentary Repository (University of Valladolid) (publishedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Hispana (submittedVersion, cc-by)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Figshare (cc-by)
- Funders
- Ministerstvo Školství, Mládeže a Tělovýchovy (CZ.1.05/2.1.00/19.0395, OP RDI CZ.1.05/2.1.00/19.0395, LM2015062-CzechBioImaging, LM2015040, LM2015062, CZ.1.05, LM2015043)
- Karolinska Institutet
- Central European Institute of Technology (LM2015043, LM2015062)
- Masarykova Univerzita (LM2015043)
- Medical Research Council (MC_PC_12009)
- European Regional Development Fund (LM2015040, CZ.1.05/2.1.00/19.0395, OP RDI CZ.1.05/2.1.00/19.0395, LM2015062)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Wnt5a, lipoprotein particles, cerebrospinal fluid, choroid plexus, cerebellar development, exosomes
- MeSH terms
- Wnt-5a Protein, Animals, Biological Transport, Choroid Plexus, Female, Humans, Lipoproteins, Male, Mice, Inbred ICR, Morphogenesis, Rhombencephalon, Signal Transduction
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