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Late neuroprogenitors contribute to normal retinal vascular development in aHif2a-dependent manner

Cristante, E; Liyanage, SE; Sampson, RD; Kalargyrou, A; De Rossi, G; Rizzi, M; Hoke, J; ... Bainbridge, JWB; + view all (2018) Late neuroprogenitors contribute to normal retinal vascular development in aHif2a-dependent manner. Development , 145 (8) , Article dev157511. 10.1242/dev.157511. Green open access

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Abstract

In the adult central nervous system, endothelial and neuronal cells engage in tight cross-talk as key components of the so-called neurovascular unit. Impairment of their critical relationship adversely affects tissue homeostasis, as observed in neurodegenerative conditions including Alzheimer's and Parkinson's disease. In development, the influence of neuroprogenitor cells on angiogenesis is poorly understood. Here, we show that these cells interact intimately with the growing retinal vascular network, and we identify a novel regulatory mechanism of vasculature development mediated by hypoxia-inducible factor 2a (Hif2a). ByCre-loxgene excision, we show thatHif2ain retinal neuroprogenitor cells upregulates the expression of the pro-angiogenic mediators vascular endothelial growth factor and erythropoietin, whereas it locally downregulates the angiogenesis inhibitor endostatin. Importantly, absence ofHif2ain retinal neuroprogenitor cells causes a marked reduction of proliferating endothelial cells at the angiogenic front. This results in delayed retinal vascular development, fewer major retinal vessels and reduced density of the peripheral deep retinal vascular plexus. Our findings demonstrate that retinal neuroprogenitor cells are a critical component of the developing neurovascular unit.

Type: Article
Title: Late neuroprogenitors contribute to normal retinal vascular development in aHif2a-dependent manner
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/dev.157511
Publisher version: https://doi.org/10.1242/dev.157511
Language: English
Additional information: © 2018. Published by The Company of Biologists Ltd. This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Angiogenesis, Cre/lox, Endostatin, Hif2a, Neuroprogenitor, Retina
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 Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
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/10046300
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