Distinct Notch signaling outputs pattern the developing arterial system
Interdisciplinary Graduate Program
Program in Gene Function and Expression
Medical Subject Headings
Animals; Animals, Genetically Modified; Arteries; Body Patterning; Cell Differentiation; Embryo, Nonmammalian; Endothelium, Vascular; Morphogenesis; Neovascularization, Physiologic; Receptors, Notch; Signal Transduction; Veins; Zebrafish
Cell and Developmental Biology | Developmental Biology
Differentiation of arteries and veins is essential for the development of a functional circulatory system. In vertebrate embryos, genetic manipulation of Notch signaling has demonstrated the importance of this pathway in driving artery endothelial cell differentiation. However, when and where Notch activation occurs to affect endothelial cell fate is less clear. Using transgenic zebrafish bearing a Notch-responsive reporter, we demonstrate that Notch is activated in endothelial progenitors during vasculogenesis prior to blood vessel morphogenesis and is maintained in arterial endothelial cells throughout larval stages. Furthermore, we find that endothelial progenitors in which Notch is activated are committed to a dorsal aorta fate. Interestingly, some arterial endothelial cells subsequently downregulate Notch signaling and then contribute to veins during vascular remodeling. Lineage analysis, together with perturbation of both Notch receptor and ligand function, further suggests several distinct developmental windows in which Notch signaling acts to promote artery commitment and maintenance. Together, these findings demonstrate that Notch acts in distinct contexts to initiate and maintain artery identity during embryogenesis.
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Citation: Development. 2014 Apr;141(7):1544-52. doi: 10.1242/dev.099986. Epub 2014 Mar 5. Link to article on publisher's site
DOI of Published Version
Development (Cambridge, England)
Quillien, Aurelie; Moore, John C.; Shin, Masahiro; Siekmann, Arndt F.; Smith, Tom; Pan, Luyuan; Moens, Cecilia B.; Parsons, Michael J.; and Lawson, Nathan D., "Distinct Notch signaling outputs pattern the developing arterial system" (2014). GSBS Student Publications. 1915.