Dual roles of the C-terminal Src kinase (Csk) during developmental vascularization.
Here we report that C-terminal Src kinase (Csk), a tyrosine kinase that negatively regulates the activity of Src and related kinases, is important for vascular development. In Csk(-/-) embryos, although vascular tubules were formed and organized into capillary-like networks during the initial genesis of blood vessels, the vessels failed to engage in normal sprout formation. In chimeric embryos containing both wild-type and Csk(-/-) cells, the presence of wild-type cells enabled Csk(-/-) endothelial cells to participate in branching morphogenesis. We suggest that wild-type cells may have supplied an angiogenic factor absent in Csk(-/-) cells. Despite the partial rescue of vascular development in chimeric embryos, the embryos failed to form vitelline vessels and died at E9.5. These results indicate that Csk is required both for angiogenic sprouting and vascular remodeling.
Duan
Li-Juan
LJ
Center for Vascular Biology, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06030-3501, USA.
Imamoto
Akira
A
Fong
Guo-Hua
GH
D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D002196:Capillaries / Q000196:embryology* / Q000502:physiology; D002678:Chimera; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases