Back to Search Start Over

Notch3 establishes brain vascular integrity by regulating pericyte number.

Authors :
Wang Y
Pan L
Moens CB
Appel B
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.

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