VA cell clusters become extraluminal. (A) VE-cadherin Cre mouse line, crossed to a R26R Cre reporter (β-galactosidase in blue), demonstrates large cell clusters from E10.0 to E10.5 that appear to migrate out of the vessel by E10.75 to E11.0 (arrows) on the caudal side of the artery. By E11.5, smaller clusters are noted on the opposite (cranial) side and proximal to the fetal liver. (B) Serial longitudinal (top) and transverse (bottom) sections through the VA at E10.25 to E10.5 show extravascular budding of the hematopoietic clusters (arrows). (C) The VA produces large clusters of HCs as traced by the VE-cadherin Cre line (β-galactosidase in blue, left panel). Semithin sections (right panels) show clusters of round cells budding from the artery (note the connection of the cluster with the VA; double arrows). A subsequent serial section (to the right) shows a cluster of cells surrounded by an endothelial layer resembling previously described mesenteric blood islands (arrow). (A-C) Scale bars as labeled per row.