title: Endothelial cells regulate neural crest and second heart field morphogenesis.
abstract: Cardiac and craniofacial developmental programs are intricately linked during early embryogenesis, which is also reflected by a high frequency of birth defects affecting both regions. The molecular nature of the crosstalk between mesoderm and neural crest progenitors and the involvement of endothelial cells within the cardio-craniofacial field are largely unclear. Here we show in the mouse that genetic ablation of vascular endothelial growth factor receptor 2 (Flk1) in the mesoderm results in early embryonic lethality, severe deformation of the cardio-craniofacial field, lack of endothelial cells and a poorly formed vascular system. We provide evidence that endothelial cells are required for migration and survival of cranial neural crest cells and consequently for the deployment of second heart field progenitors into the cardiac outflow tract. Insights into the molecular mechanisms reveal marked reduction in Transforming growth factor beta 1 (Tgfb1) along with changes in the extracellular matrix (ECM) composition. Our collective findings in both mouse and avian models suggest that endothelial cells coordinate cardio-craniofacial morphogenesis, in part via a conserved signaling circuit regulating ECM remodeling by Tgfb1.
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Milgrom-Hoffman
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Inbal
authors.initials: I
authors.lastname: Michailovici
authors.affiliation: Department of Pathology, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Napoleone
authors.initials: N
authors.lastname: Ferrara
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Elazar
authors.initials: E
authors.lastname: Zelzer
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel eldad.tzahor@weizmann.ac.il.
authors.forename: Eldad
authors.initials: E
authors.lastname: Tzahor
keywords: ECM; Endothelial cell; Neural crest; Second heart field