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MEIS-WNT5A axis regulates development of fourth ventricle choroid plexus.
- Source :
-
Development (Cambridge, England) [Development] 2021 May 15; Vol. 148 (10). Date of Electronic Publication: 2021 May 25. - Publication Year :
- 2021
-
Abstract
- The choroid plexus (ChP) produces cerebrospinal fluid and forms an essential brain barrier. ChP tissues form in each brain ventricle, each one adopting a distinct shape, but remarkably little is known about the mechanisms underlying ChP development. Here, we show that epithelial WNT5A is crucial for determining fourth ventricle (4V) ChP morphogenesis and size in mouse. Systemic Wnt5a knockout, or forced Wnt5a overexpression beginning at embryonic day 10.5, profoundly reduced ChP size and development. However, Wnt5a expression was enriched in Foxj1-positive epithelial cells of 4V ChP plexus, and its conditional deletion in these cells affected the branched, villous morphology of the 4V ChP. We found that WNT5A was enriched in epithelial cells localized to the distal tips of 4V ChP villi, where WNT5A acted locally to activate non-canonical WNT signaling via ROR1 and ROR2 receptors. During 4V ChP development, MEIS1 bound to the proximal Wnt5a promoter, and gain- and loss-of-function approaches demonstrated that MEIS1 regulated Wnt5a expression. Collectively, our findings demonstrate a dual function of WNT5A in ChP development and identify MEIS transcription factors as upstream regulators of Wnt5a in the 4V ChP epithelium.<br />Competing Interests: Competing interests The authors declare no competing or financial interests.<br /> (© 2021. Published by The Company of Biologists Ltd.)
- Subjects :
- Animals
Brain embryology
CRISPR-Cas Systems genetics
Cell Line
Epithelial Cells metabolism
Female
HEK293 Cells
Humans
Mice
Mice, Knockout
Promoter Regions, Genetic genetics
Receptor Tyrosine Kinase-like Orphan Receptors metabolism
Signal Transduction physiology
Wnt-5a Protein genetics
Choroid Plexus embryology
Epithelium metabolism
Fourth Ventricle embryology
Myeloid Ecotropic Viral Integration Site 1 Protein metabolism
Wnt-5a Protein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9129
- Volume :
- 148
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Development (Cambridge, England)
- Publication Type :
- Academic Journal
- Accession number :
- 34032267
- Full Text :
- https://doi.org/10.1242/dev.192054