p120-Catenin is required for mouse vascular development.
BACKGROUND
p120-catenin (p120) is an armadillo family protein that binds to the cytoplasmic domain of classical cadherins and prevents cadherin endocytosis. The role of p120 in vascular development is unknown.


OBJECTIVE
The purpose of this study is to examine the role of p120 in mammalian vascular development by generating a conditionally mutant mouse lacking endothelial p120 and determining the effects of the knockout on vasculogenesis, angiogenic remodeling, and the regulation of endothelial cadherin levels.


RESULTS
A conditional Cre/loxP gene deletion strategy was used to ablate p120 expression, using the Tie2 promoter to drive endothelial Cre recombinase expression. Mice lacking endothelial p120 died embryonically beginning at embryonic day 11.5. Major blood vessels appeared normal at embryonic day 9.5. However, both embryonic and extraembryonic vasculature of mutant animals were disorganized and displayed decreased microvascular density by embryonic day 11.5. Importantly, both vascular endothelial cadherin and N-cadherin levels were significantly reduced in vessels lacking p120. This decrease in cadherin expression was accompanied by reduced pericyte recruitment and hemorrhaging. Furthermore, p120-null cultured endothelial cells exhibited proliferation defects that could be rescued by exogenous expression of vascular endothelial cadherin.


CONCLUSIONS
These findings reveal a fundamental role for p120 in regulating endothelial cadherin levels during vascular development, as well as microvascular patterning, vessel integrity, and endothelial cell proliferation. Loss of endothelial p120 results in lethality attributable to decreased microvascular density and hemorrhages.
Oas
Rebecca G
RG
Department of Cell Biology, 615 Michael St, Room 465, Atlanta, GA 30322, USA.
Xiao
Kanyan
K
Summers
Susan
S
Wittich
Kristin B
KB
Chiasson
Christine M
CM
Martin
W David
WD
Grossniklaus
Hans E
HE
Vincent
Peter A
PA
Reynolds
Albert B
AB
Kowalczyk
Andrew P
AP
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001808:Blood Vessels / Q000196:embryology* / Q000378:metabolism* / Q000473:pathology; D019521:Body Patterning; D016827:CD8 Antigens; D015820:Cadherins / Q000378:metabolism; D051177:Catenins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D020964:Embryo Loss; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005865:Gestational Age; D006470:Hemorrhage / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D007136:Immunoglobulins; D019426:Integrases / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055806:Microvessels / Q000196:embryology / Q000378:metabolism; D020286:Pericytes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D042787:Receptor, TIE-2; D000095002:Delta Catenin; D000099152:Cadherin 5
D015703:Antigens, CD; D016827:CD8 Antigens; D015820:Cadherins; D051177:Catenins; D007136:Immunoglobulins; D019426:Integrases; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; D000095002:Delta Catenin; D000099152:Cadherin 5; C489083:Cdh2 protein, mouse; C115408:IGSF6 protein, human; C079086:Tek protein, mouse; C045073:Cre recombinase; C000722349:Ctnnd1 protein, mouse