Canonical Wnt Signaling Regulates Organ-Specific Assembly and Differentiation of CNS Vasculature
Abstract
Every organ depends on blood vessels for oxygen and nutrients, but the vasculature associated with individual organs can be structurally and molecularly diverse. The central nervous system (CNS) vasculature consists of a tightly sealed endothelium that forms the blood-brain barrier, whereas blood vessels of other organs are more porous. Wnt7a and Wnt7b encode two Wnt ligands produced by the neuroepithelium of the developing CNS coincident with vascular invasion. Using genetic mouse models, we found that these ligands directly target the vascular endothelium and that the CNS uses the canonical Wnt signaling pathway to promote formation and CNS-specific differentiation of the organ's vasculature.
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Wnt signaling pathway including Wnt ligands, Norrins, Frizzled receptors, Lrp5/6 coreceptors, Gpr124 and Reck cofactors, and β-catenin are critical for both vascular development and barriergenesis.
“Wnt signaling pathway including Wnt ligands, Norrins, Frizzled receptors, Lrp5/6 coreceptors, Gpr124 and Reck cofactors, and 𝛃 -catenin are critical for both vascular development and barriergenesis (138, 332, 558, 636, 682, 689);”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [558]
During embryogenesis, neural progenitor cells can secrete Wnt ligands to regulate development of brain vasculature and BBB through activation of canonical Wnt signaling in ECs.
“During embryogenesis, neural progenitor cells can secrete Wnt ligands to regulate the development of brain vasculature and BBB through activation of canonical Wnt signaling in ECs6,7.”
From Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity (2017) · cites this paper as [6]
During embryogenesis, neural progenitors secrete Wnt ligands, which activate canonical Wnt signaling in ECs and contribute to maturation of brain vasculature.
“During embryogenesis, neural progenitors secrete Wnt ligands, which activate canonical Wnt signaling in ECs and contribute to the maturation of brain vasculature6,7,8.”
From Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity (2017) · cites this paper as [6]
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- Authors
- Stenman, J. M., Rajagopal, J., Carroll, T. J., Ishibashi, M., McMahon, J., & McMahon, A. P.
- Affiliations
- Harvard University (US)
- Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
- Corresponding author
- Stenman, Jan M.
- Carroll, Thomas J.
- McMahon, Andrew P.
- Venue
- Science
- Published
- 2008-11-21
- Volume
- 322
- Issue
- 5905
- Pages
- 1247-1250
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2032112615
- Cited by
- 641
- References
- 0
- Citations by year
- 2026: 27 · 2025: 38 · 2024: 38 · 2023: 31 · 2022: 51 · 2021: 32 · 2020: 48 · 2019: 43 · 2018: 39 · 2017: 51 · 2016: 30 · 2015: 46 · 2014: 43 · 2013: 28 · 2012: 25
- FWCI
- 15.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (K08HL076393, HL076393)
- National Institute of Diabetes and Digestive and Kidney Diseases ([DK054364, R37DK054364)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Wnt signaling, Wnt7a, Wnt7b, blood-brain barrier, vascular endothelium, neuroepithelium, vascular invasion, endothelial differentiation
- MeSH terms
- Animals, Blood-Brain Barrier, Central Nervous System, Embryonic Induction, Mutation, Proto-Oncogene Proteins, Signal Transduction, Neovascularization, Physiologic, Neuroepithelial Cells, Wnt Proteins, beta Catenin, Mice
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