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Foxf2 Is Required for Brain Pericyte Differentiation and Development and Maintenance of the Blood-Brain Barrier

Journal article
Authors Azadeh Reyahi
Ali Moussavi Nik
Mozhgan Ghiami
Amel Gritli Linde
F. Ponten
Bengt R Johansson
Peter Carlsson
Published in Developmental Cell
Volume 34
Issue 1
Pages 19-32
ISSN 1534-5807
Publication year 2015
Published at Institute of Odontology
Institute of Biomedicine
Department of Chemistry and Molecular Biology
Pages 19-32
Language en
Links dx.doi.org/10.1016/j.devcel.2015.05...
Keywords WHITE-MATTER ABNORMALITIES, SMOOTH-MUSCLE-CELLS, TAMOXIFEN-INDUCIBLE, FORM, CREST-DERIVED CELLS, GROWTH-FACTOR-BETA, NEURAL CREST, 6P25, DELETION, MOUSE EMBRYOS, MICE LACKING, PDGF-B, Cell Biology, Developmental Biology
Subject categories Cell and Molecular Biology

Abstract

Pericytes are critical for cerebrovascular maturation and development of the blood-brain barrier (BBB), but their role in maintenance of the adult BBB, and how CNS pericytes differ from those of other tissues, is less well understood. We show that the forkhead transcription factor Foxf2 is specifically expressed in pericytes of the brain and that Foxf2(-/-) embryos develop intracranial hemorrhage, perivascular edema, thinning of the vascular basal lamina, an increase of luminal endothelial caveolae, and a leaky BBB. Foxf2(-/-) brain pericytes were more numerous, proliferated faster, and expressed significantly less Pdgfr beta. Tgf beta-Smad2/3 signaling was attenuated, whereas phosphorylation of Smad1/5 and p38 were enhanced. Tgf beta pathway components, including Tgf beta 2, Tgf beta r2, Alk5, and integrins alpha(V)beta(8), were reduced. Foxf2 inactivation in adults resulted in BBB breakdown, endothelial thickening, and increased trans-endothelial vesicular transport. On the basis of these results, FOXF2 emerges as an interesting candidate locus for stroke susceptibility in humans.

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Denna text är utskriven från följande webbsida:
http://www.gu.se/english/research/publication/?publicationId=220142
Utskriftsdatum: 2019-09-19