Fig. 8. Endothelial cell signaling regulates the morphogenesis of the cardio–craniofacial field.

(A) Endothelial cells (blue) are scattered throughout the entire dorso-ventral axis of the embryo, underlying the neural tube and entering the heart. Neural crest cells (green) follow the same path and enter only the most arterial pole of the OFT together with SHF progenitors (yellow). (B) The cranial progenitor niche. ECs secrete Tgfb1 that balances secretion of Loxl2 and enables proper remodeling of the ECM. (C) Loss of ECs results in reduction of Tgfb signaling and increased levels of Loxl2. Here, the ECM loses its integrity causing migratory defects of NC and SHF progenitors together with reduction in proliferation of the neuroepithelium. (D) ECM remodeling is mediated by signaling from progenitors, which in turn rely on ECM integrity for proper migration and consequent morphogenesis. nt, neural tube.