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Notch3 establishes brain vascular integrity by regulating pericyte number.
- Source :
-
Development (Cambridge, England) [Development] 2014 Jan; Vol. 141 (2), pp. 307-17. Date of Electronic Publication: 2013 Dec 04. - Publication Year :
- 2014
-
Abstract
- Brain pericytes are important regulators of brain vascular integrity, permeability and blood flow. Deficiencies of brain pericytes are associated with neonatal intracranial hemorrhage in human fetuses, as well as stroke and neurodegeneration in adults. Despite the important functions of brain pericytes, the mechanisms underlying their development are not well understood and little is known about how pericyte density is regulated across the brain. The Notch signaling pathway has been implicated in pericyte development, but its exact roles remain ill defined. Here, we report an investigation of the Notch3 receptor using zebrafish as a model system. We show that zebrafish brain pericytes express notch3 and that notch3 mutant zebrafish have a deficit of brain pericytes and impaired blood-brain barrier function. Conditional loss- and gain-of-function experiments provide evidence that Notch3 signaling positively regulates brain pericyte proliferation. These findings establish a new role for Notch signaling in brain vascular development whereby Notch3 signaling promotes expansion of the brain pericyte population.
- Subjects :
- Animals
Animals, Genetically Modified
Blood-Brain Barrier growth & development
Blood-Brain Barrier metabolism
Brain blood supply
Cell Count
Cell Differentiation
Cell Proliferation
Cerebral Hemorrhage etiology
Cerebral Hemorrhage genetics
Cerebral Hemorrhage metabolism
Gene Expression Regulation, Developmental
Humans
Mutation
Receptor, Notch3
Receptor, Platelet-Derived Growth Factor beta genetics
Receptor, Platelet-Derived Growth Factor beta metabolism
Receptors, Notch deficiency
Receptors, Notch genetics
Signal Transduction
Zebrafish genetics
Zebrafish Proteins deficiency
Zebrafish Proteins genetics
Brain growth & development
Brain metabolism
Pericytes cytology
Pericytes metabolism
Receptors, Notch metabolism
Zebrafish growth & development
Zebrafish metabolism
Zebrafish Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9129
- Volume :
- 141
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Development (Cambridge, England)
- Publication Type :
- Academic Journal
- Accession number :
- 24306108
- Full Text :
- https://doi.org/10.1242/dev.096107