The widely accepted model of angiogenic sprouting proposes that a single cell – the tip cell – is found at the leading edge of vessel sprouts. Now, Victoria Bautch and colleagues describe an alternative blood vessel topology in which multiple endothelial cells (ECs) constitute the tip of sprouting blood vessels and polarize to promote lumen formation (p. 4121). By mosaically labelling ECs in both in vitro and in vivo angiogenesis assays, the researchers first demonstrate that sprouts often contain two cells at their tips, and that both cells extend filopodia. Live imaging studies show that, as reported previously, these tip cells switch positions, but the cell-cell overlap is largely maintained throughout switching. The researchers further report that tip cells polarize along their longitudinal cell-cell border; this border is characterized by apical polarity markers and is the site of lumen formation. Finally, the authors show that the loss of an atypical protein kinase C (aPKC) isoform disrupts EC overlap and lumen formation, highlighting a role for aPKC in angiogenic sprouting. Together, these observations suggest that the paradigm of a single cell at the tip of developing blood vessels requires revision.
Two top tips for angiogenesis
Two top tips for angiogenesis. Development 1 November 2014; 141 (21): e2101. doi:
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