Abstract:
:The cerebral cortex performs complex cognitive functions at the expense of tremendous energy consumption. Blood vessels in the brain are known to form stereotypic patterns that facilitate efficient oxygen and nutrient delivery. Yet little is known about how vessel development in the brain is normally regulated. Radial glial neural progenitors are well known for their central role in orchestrating brain neurogenesis. Here we show that, in the late embryonic cortex, radial glial neural progenitors also play a key role in brain angiogenesis, by interacting with nascent blood vessels and regulating vessel stabilization via modulation of canonical Wnt signaling. We find that ablation of radial glia results in vessel regression, concomitant with ectopic activation of Wnt signaling in endothelial cells. Direct activation of Wnt signaling also results in similar vessel regression, while attenuation of Wnt signaling substantially suppresses regression. Radial glial ablation and ectopic Wnt pathway activation leads to elevated endothelial expression of matrix metalloproteinases, while inhibition of metalloproteinase activity significantly suppresses vessel regression. These results thus reveal a previously unrecognized role of radial glial progenitors in stabilizing nascent brain vascular network and provide novel insights into the molecular cascades through which target neural tissues regulate vessel stabilization and patterning during development and throughout life.
journal_name
PLoS Bioljournal_title
PLoS biologyauthors
Ma S,Kwon HJ,Johng H,Zang K,Huang Zdoi
10.1371/journal.pbio.1001469subject
Has Abstractpub_date
2013-01-01 00:00:00pages
e1001469issue
1eissn
1544-9173issn
1545-7885pii
PBIOLOGY-D-12-02446journal_volume
11pub_type
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