MAILMAN RESEARCH CENTER
Angiogenesis & Brain Development Laboratory
(A) Immunohistochemical labeling for blood vessels (Isolectin B4-green), bromodeoxyuridine (BrdU, 2.0 hr exposure, red/pink) and stem/progenitor cell marker Musashi (blue) in a 20 µm-thick coronal paraffin section through E11 mouse telencephalon. The periventricular vessel developmental gradient (white arrows) is apparent in the dorsal telencephalon while the pial vessels encircle the entire telencephalon (orange arrows). (B) Periventricular and pial vascular networks are very closely associated with the deep (white arrows) and superficial (yellow arrows) streams of GABA neurons in the embryonic telencephalon. (C-D) The periventricular angiogenesis gradient is significantly related to the GABA neuron gradient at mechanistic levels. One example is depicted here in high (C) and low (D) magnification images of periventricular endothelial cells (labeled with isolectin B4-red) expressing GABAA Receptor (GABRB3-green). (E-F) Specific deletion of VEGF from endothelial cells (Vegf ΔTie2-Cremice) reveals an autonomous role of endothelial cell-derived VEGF that impacts neuronal proliferation, migration and eventually the telencephalic cytoarchitecture. Ki67+ve proliferating progenitors (green) infiltrated cortical plate ectopias (yellow arrows), breakdown of pial membrane with concurrent neuronal over-migration (pink arrow) and disruption of the ventricular zone continuity (red arrow) were observed in E17 Vegf ΔTie2-Cre telencephalon, reminiscent of cobblestone lissencephaly (E). Abnormal crests and grooves of MAP2+ve cells revealed intense polymicrogyria (yellow arrows) in E17 Vegf ΔTie2-Cre telencephalon (F). DAPI was used to label nuclei (C-F). Scale bars: A â€“ 100 µm (applies to B, E and F), 50 µm (D), 15 µm (C). Our studies aim at understanding the intimate and symbiotic relationship between endothelial cells and neurons of the CNS from developmental and disease perspectives.
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