ZFIN ID: ZDB-PUB-161122-3
Asymmetric division coordinates collective cell migration in angiogenesis
Costa, G., Harrington, K.I., Lovegrove, H.E., Page, D.J., Chakravartula, S., Bentley, K., Herbert, S.P.
Date: 2016
Source: Nature cell biology   18(12): 1292-1301 (Journal)
Registered Authors: Herbert, Shane
Keywords: Angiogenesis, Cell division, Mitotic spindle, Zebrafish
MeSH Terms:
  • Animals
  • Asymmetric Cell Division*
  • Cell Movement*
  • Cell Polarity
  • Cell Size
  • Computer Simulation
  • Endothelial Cells/cytology
  • Endothelial Cells/metabolism
  • Green Fluorescent Proteins/metabolism
  • Mitosis
  • Neovascularization, Physiologic*
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Receptors, Notch
  • Receptors, Vascular Endothelial Growth Factor/metabolism
  • Signal Transduction
  • Time-Lapse Imaging
  • Zebrafish
  • Zebrafish Proteins/metabolism
PubMed: 27870831 Full text @ Nat. Cell Biol.
The asymmetric division of stem or progenitor cells generates daughters with distinct fates and regulates cell diversity during tissue morphogenesis. However, roles for asymmetric division in other more dynamic morphogenetic processes, such as cell migration, have not previously been described. Here we combine zebrafish in vivo experimental and computational approaches to reveal that heterogeneity introduced by asymmetric division generates multicellular polarity that drives coordinated collective cell migration in angiogenesis. We find that asymmetric positioning of the mitotic spindle during endothelial tip cell division generates daughters of distinct size with discrete 'tip' or 'stalk' thresholds of pro-migratory Vegfr signalling. Consequently, post-mitotic Vegfr asymmetry drives Dll4/Notch-independent self-organization of daughters into leading tip or trailing stalk cells, and disruption of asymmetry randomizes daughter tip/stalk selection. Thus, asymmetric division seamlessly integrates cell proliferation with collective migration, and, as such, may facilitate growth of other collectively migrating tissues during development, regeneration and cancer invasion.