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J Neurosci. 2013 Sep 11;33(37):14809-15. doi: 10.1523/JNEUROSCI.1368-13.2013.

Endothelial VEGF sculpts cortical cytoarchitecture.

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Angiogenesis and Brain Development Laboratory, Division of Basic Neuroscience, McLean Hospital/Harvard Medical School, Belmont, Massachusetts 02478, Vascular Cell Biology Unit, Department for Molecular Biomedical Research, VIB, B-9052 Ghent, Belgium, Department for Biomedical Molecular Biology, Ghent University, B-9052 Ghent, Belgium, and Australian Centre for Blood Diseases, Monash University, Melbourne, VIC 3004, Australia.


Current models of brain development support the view that VEGF, a signaling protein secreted by neuronal cells, regulates angiogenesis and neuronal development. Here we demonstrate an autonomous and pivotal role for endothelial cell-derived VEGF that has far-reaching consequences for mouse brain development. Selective deletion of Vegf from endothelial cells resulted in impaired angiogenesis and marked perturbation of cortical cytoarchitecture. Abnormal cell clusters or heterotopias were detected in the marginal zone, and disorganization of cortical cells induced several malformations, including aberrant cortical lamination. Critical events during brain development-neuronal proliferation, differentiation, and migration were significantly affected. In addition, axonal tracts in the telencephalon were severely defective in the absence of endothelial VEGF. The unique roles of endothelial VEGF cannot be compensated by neuronal VEGF and underscores the high functional significance of endothelial VEGF for cerebral cortex development and from disease perspectives.

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