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Cell‐autonomous notch signaling regulates endothelial cell branching and proliferation during vascular tubulogenesis
Author(s) -
Sainson Richard C. A.,
Aoto Jason,
Nakatsu Martin N.,
Holderfield Matthew,
Conn Erin,
Koller Erich,
Hughes Christopher C. W.
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-3172fje
Subject(s) - notch signaling pathway , microbiology and biotechnology , angiogenesis , hes3 signaling axis , notch proteins , biology , embryonic stem cell , cell polarity , endothelial stem cell , cell , signal transduction , genetics , in vitro , gene
The requirement for notch signaling during vascular development is well‐documented but poorly understood. Embryonic and adult endothelial cells (EC) express notch and notch ligands; however, the necessity for cell‐autonomous notch signaling during angiogenesis has not been determined. During angiogenesis, EC display plasticity, whereby a subset of previously quiescent cells loses polarity and becomes migratory. To investigate the role of notch in EC, we have used a three‐dimensional in vitro system that models all of the early steps of angiogenesis. We find that newly forming sprouts are composed of specialized tip cells that guide the sprout and trunk cells that proliferate and rearrange to form intercellular lumens. Furthermore, we find that notch acts cell‐autonomously to suppress EC proliferation, thereby regulating tube diameter. In addition, when notch signaling is blocked, tip cells divide, and both daughter cells take on a tip cell phenotype, resulting in increased branching through vessel bifurcation. In contrast, notch signaling is not required for re‐establishment of EC polarity or for lumen formation. Thus, notch is used reiteratively and cell‐autonomously by EC to regulate vessel diameter, to limit branching at the tip of sprouts, and to establish a mature, quiescent phenotype.