Cranial Neural Crest Migration Sculpts Endothelial Patterning in Avians with Anti‐Angiogenic Factors

Abstract

The embryonic neural crest and endothelial cells arise in separate locations but migrate to form intimately‐linked distinct structures in the vertebrate head. The lack of in vivo observations of these cell populations simultaneously in the same embryo has led to several unanswered mechanistic questions. Here, we take advantage of fluorescent labeling of cranial neural crest cells within Tie1 transgenic quail embryos Tg(tie1:H2B‐eYFP) to examine the dynamics of cranial neural crest and endothelial cell migration. In vivo time‐lapse analysis reveals that migrating neural crest and endothelial cells 1) move in opposing directions along a common dorsolateral migratory pathway, 2) display physical interactions that result in changes mainly in endothelial cell trajectories, 3) sort onto discrete pathways after interacting. Deletion of premigratory cranial neural crest cells results in changes to the endothelial cell movements and the vascular pattern. To examine the underlying molecular signals, we find that neural crest cells express anti‐angiogenic factors confirmed by fluorescence in‐situ hybridization and protein analysis. We specifically test the role of Angiopoetin‐2 and show that gain‐ or loss‐of‐function in neural crest cells leads to alterations in the migration patterns of the neural crest and endothelial cells. Together, our data support a model hypothesis that migrating neural crest cells express anti‐angiogenic factors in order to prevent occlusion of their migration by premature vessel formationSupport or Funding InformationStowers Institute for Medical Research