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Wasp controls oriented migration of endothelial cells to achieve functional vascular patterning

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Item Type:Preprint
Title:Wasp controls oriented migration of endothelial cells to achieve functional vascular patterning
Creators Name:Rosa, A. and Giese, W. and Meier, K. and Alt, S. and Klaus-Bergmann, A. and Edgar, L.T. and Bartels, E. and Collins, R. and Szymborska-Mell, A. and Coxam, B. and Bernabeu, M.O. and Gerhardt, H.
Abstract:Endothelial cell migration and proliferation are essential for the establishment of a hierarchical organization of blood vessels and optimal distribution of blood. However, how these cellular processes are coordinated remains unknown. Here, using the zebrafish trunk vasculature we show that in future veins endothelial cells proliferate more than in future arteries and migrate preferentially towards neighboring arteries. In future arteries endothelial cells show a biphasic migration profile. During sprouting cells move away from the dorsal aorta, during remodelling cells stop or move towards the feeding aorta. The final morphology of blood vessels is thus established by local proliferation and oriented cell migration to and from neighboring vessels. Additionally, we identify WASp to be essential for this differential migration. Loss of WASp leads to irregular distribution of endothelial cells, substantially enlarged veins and persistent arteriovenous shunting. Mechanistically, we report that WASp drives the assembly of junctional associated actin filaments and is required for junctional expression of PECAM-1. Together, our data identify that functional vascular patterning in the zebrafish trunk utilizes differential cell movement regulated by junctional actin, and that interruption of differential migration may represent a pathomechanism in vascular malformations.
Keywords:Migration, Proliferation, WASp, F-actin, Vessel Remodelling, Animals, Zebrafish
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2020.09.15.296574
Date:15 September 2020
Official Publication:https://doi.org/10.1101/2020.09.15.296574
Related to:
https://edoc.mdc-berlin.de/21167/Final version

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