Open Accessc-Src controls stability of sprouting blood vessels in the developing retina independently of cell-cell adhesion through focal adhesion assembly
Author(s) -
Lilian Schimmel,
Daisuke Fukuhara,
Mark Richards,
Yi Jin,
Patricia Essebier,
Emmanuelle Frampton,
Marie Hedlund,
Elisabetta Dejana,
Lena ClaessonWelsh,
Emma Gordon
Publication year - 2020
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.15
H-Index - 36
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.185405
Subject(s) - adherens junction , sprouting angiogenesis , microbiology and biotechnology , biology , focal adhesion , angiogenesis , proto oncogene tyrosine protein kinase src , cell adhesion , adhesion , endothelial stem cell , cadherin , neovascularization , cell , signal transduction , cancer research , chemistry , biochemistry , in vitro , organic chemistry
Endothelial cell adhesion is implicated in blood vessel sprout formation, yet how adhesion controls angiogenesis, and whether it occurs via rapid remodeling of adherens junctions or focal adhesion assembly, or both, remains poorly understood. Furthermore, how endothelial cell adhesion is controlled in particular tissues and under different conditions remains unexplored. Here, we have identified an unexpected role for spatiotemporal c-Src activity in sprouting angiogenesis in the retina, which is in contrast to the dominant focus on the role of c-Src in the maintenance of vascular integrity. Thus, mice specifically deficient in endothelial c-Src displayed significantly reduced blood vessel sprouting and loss in actin-rich filopodial protrusions at the vascular front of the developing retina. In contrast to what has been observed during vascular leakage, endothelial cell-cell adhesion was unaffected by loss of c-Src. Instead, decreased angiogenic sprouting was due to loss of focal adhesion assembly and cell-matrix adhesion, resulting in loss of sprout stability. These results demonstrate that c-Src signaling at specified endothelial cell membrane compartments (adherens junctions or focal adhesions) control vascular processes in a tissue- and context-dependent manner.