Jadon Julian, Yelin Ronit, Arraf Alaa A, Asleh Manar Abboud, Zaher Mira, Schultheiss Thomas M
Department of Genetics and Developmental Biology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, 31096, Israel.
Department of Genetics and Developmental Biology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, 31096, Israel.
Dev Biol. 2023 May;497:1-10. doi: 10.1016/j.ydbio.2023.02.006. Epub 2023 Feb 24.
In amniote vertebrates, the definitive dorsal aorta is formed by the fusion of two primordial aortic endothelial tubes. Formation of the definitive dorsal aorta requires extensive cellular migrations and rearrangements of the primordial tubes in order to generate a single vessel located at the embryonic ventral midline. This study examines the role of VEGF signaling in the generation of the definitive dorsal aorta. Through gain- and loss-of-function studies in vivo in the chick embryo, we document a requirement for VEGF signaling in growth and remodeling of the paired primordia. We find that regions of the aorta are differentially sensitive to levels of VEGF signaling, and present evidence that areas of low blood flow are more sensitive to the loss of VEGF signaling. We also find that VEGF signaling regulates the intracellular distribution between membrane and cytoplasm of the cell-cell adhesion molecule VE-cadherin in aortic endothelial cells in vivo. Together, these finding identify mechanisms that likely contribute to the dynamic behavior of endothelial cells during aorta morphogenesis.
在羊膜动物中,定型背主动脉由两条原始主动脉内皮管融合形成。定型背主动脉的形成需要原始管进行广泛的细胞迁移和重排,以生成位于胚胎腹中线的单一血管。本研究探讨了VEGF信号在定型背主动脉生成中的作用。通过在鸡胚体内进行功能获得和功能丧失研究,我们证明了VEGF信号在成对原基的生长和重塑中是必需的。我们发现主动脉区域对VEGF信号水平的敏感性不同,并且有证据表明低血流区域对VEGF信号丧失更敏感。我们还发现VEGF信号在体内调节主动脉内皮细胞中细胞间粘附分子VE-钙粘蛋白在细胞膜和细胞质之间的细胞内分布。这些发现共同确定了可能有助于主动脉形态发生过程中内皮细胞动态行为的机制。