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Publication : Endothelial cells regulate neural crest and second heart field morphogenesis.

First Author  Milgrom-Hoffman M Year  2014
Journal  Biol Open Volume  3
Issue  8 Pages  679-88
PubMed ID  24996922 Mgi Jnum  J:214961
Mgi Id  MGI:5604299 Doi  10.1242/bio.20148078
Citation  Milgrom-Hoffman M, et al. (2014) Endothelial cells regulate neural crest and second heart field morphogenesis. Biol Open 3(8):679-88
abstractText  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.
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