1. ADAMTS18 Modulates the Development of Aortic Arch and Common Carotid Artery
- Author
-
Yi-Hsuan Pan, Taojing Wu, Tiantian Lu, Xiaobing Yuan, Thomas Wisniewski, Liya Wang, Suying Dang, Shuai Ye, Xiaohua Cao, Wei Zhang, and Ning Yang
- Subjects
Aortic arch ,Vascular smooth muscle ,biology ,ADAMTS ,Cell biology ,Fibronectin ,Extracellular matrix ,Cranial neural crest ,medicine.anatomical_structure ,medicine.artery ,cardiovascular system ,biology.protein ,medicine ,Carotid body ,Common carotid artery - Abstract
ADAMTS members have been implicated in vascular diseases by degrading extracellular matrix (ECM), but their functional significance in vascular development remains unknown. We now show that the secreted protease ADAMTS18 is produced by mesenchymal cells and fibroblasts surrounding the embryonic aortic arch (AOAR) and the common carotid artery (CCA). ADAMTS18 deficiency leads to aberrant AOAR and CCA, which further disturbs the development of the 3rd and 4th branchial arch appendages, leading to lack of formation of the carotid body, generation of ectopic and hypoplastic thymus, and variation of intracranial vascular branches of CCA. ADAMTS18 was shown to modulate the ECM abundance around AOAR and CCA, in particular fibronectin (Fn). Adamts18 deficiency lead to Fn accumulation, thus activating the Notch3 signaling pathway to promote the differentiation of cranial neural crest cells (CNCCs) to vascular smooth muscle cells. These data disclose that ADAMTS18-mediated ECM homeostasis is crucial for the differentiation of CNCCs.
- Published
- 2021