Open AccessWASp controls oriented migration of endothelial cells to achieve functional vascular patterning
Author(s) -
André Rosa,
Wolfgang Giese,
Katja Meier,
Silvanus Alt,
Alexandra KlausBergmann,
Lowell T. Edgar,
Eireen BartelsKlein,
Russell T. Collins,
Anna Szymborska,
Baptiste Coxam,
Miguel O. Bernabéu,
Holger Gerhardt
Publication year - 2022
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.200195
Subject(s) - biology , zebrafish , microbiology and biotechnology , cell migration , morphogenesis , regulator , anatomy , mural cell , actin , endothelial stem cell , cell , gene , genetics , in vitro
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 quantitatively coordinated to drive vascular network morphogenesis remains unknown. Here, using the zebrafish vasculature as a model system, we demonstrate that the balanced distribution of endothelial cells, as well as the resulting regularity of vessel calibre, is a result of cell migration from veins towards arteries and cell proliferation in veins. We identify the Wiskott-Aldrich Syndrome protein (WASp) as an important molecular regulator of this process and show that loss of coordinated migration from veins to arteries upon wasb depletion results in aberrant vessel morphology and the formation of persistent arteriovenous shunts. We demonstrate that WASp achieves its function through the coordination of junctional actin assembly and PECAM1 recruitment and provide evidence that this is conserved in humans. Overall, we demonstrate that functional vascular patterning in the zebrafish trunk is established through differential cell migration regulated by junctional actin, and that interruption of differential migration may represent a pathomechanism in vascular malformations.