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Vascular-derived Vegfa promotes cortical interneuron migration and proximity to the vasculature in the developing forebrain

Barber, M; Andrews, WD; Memi, F; Gardner, P; Ciantar, D; Tata, M; Ruhrberg, C; (2018) Vascular-derived Vegfa promotes cortical interneuron migration and proximity to the vasculature in the developing forebrain. Cerebral Cortex , 28 (7) pp. 2577-2593. 10.1093/cercor/bhy082. Green open access

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Abstract

Vascular endothelial growth factor (Vegfa) is essential for promoting the vascularization of the embryonic murine forebrain. In addition, it directly influences neural development, although its role in the forming forebrain is less well elucidated. It was recently suggested that Vegfa may influence the development of GABAergic interneurons, inhibitory cells with crucial signaling roles in cortical neuronal circuits. However, the mechanism by which it affects interneuron development remains unknown. Here we investigated the developmental processes by which Vegfa may influence cortical interneuron development by analyzing transgenic mice that ubiquitously express the Vegfa120 isoform to perturb its signaling gradient. We found that interneurons reach the dorsal cortex at mid phases of corticogenesis despite an aberrant vascular network. Instead, endothelial ablation of Vegfa alters cortical interneuron numbers, their intracortical distribution and spatial proximity to blood vessels. We show for the first time that vascular-secreted guidance factors promote early-migrating interneurons in the intact forebrain in vivo and identify a novel role for vascular-Vegfa in this process.

Type: Article
Title: Vascular-derived Vegfa promotes cortical interneuron migration and proximity to the vasculature in the developing forebrain
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/cercor/bhy082
Publisher version: https://doi.org/10.1093/cercor/bhy082
Language: English
Additional information: © The Author(s) 2018. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Supplementa
Keywords: cortical development, GABAergic interneurons, neurovascular coupling, Vegfa
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10047666
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