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Cold Spring Harb Perspect Med. 2012 Feb;2(2):a006601. doi: 10.1101/cshperspect.a006601.

Tips, stalks, tubes: notch-mediated cell fate determination and mechanisms of tubulogenesis during angiogenesis.

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  • 1Department of Obstetrics/Gynecology and Pathology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York 10032, USA.


Angiogenesis is the process of developing vascular sprouts from existing blood vessels. Luminal endothelial cells convert into "tip" cells that contribute to the development of a multicellular stalk, which then undergoes lumen formation. In this review, we consider a variety of cellular and molecular pathways that mediate these transitions. We focus first on Notch signaling in cell fate determination as a mechanism to define tip and stalk cells. We next discuss the current models of lumen formation and describe new players in this process, such as chloride intracellular channel proteins. Finally, we consider the possible medical therapeutic benefits of understanding these processes and acknowledge potential obstacles in drug development.

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