Adamts18 modulates the development of the aortic arch and common carotid artery
Shuai Ye,
Ning Yang,
Tiantian Lu,
Taojing Wu,
Liya Wang,
Yi-Hsuan Pan,
Xiaohua Cao,
Xiaobing Yuan,
Thomas Wisniewski,
Suying Dang,
Wei Zhang
Affiliations
Shuai Ye
Key Laboratory of Brain Functional Genomics (Ministry of Education and Shanghai), School of Life Sciences, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China
Ning Yang
Key Laboratory of Brain Functional Genomics (Ministry of Education and Shanghai), School of Life Sciences, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China
Tiantian Lu
Key Laboratory of Brain Functional Genomics (Ministry of Education and Shanghai), School of Life Sciences, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China
Taojing Wu
Key Laboratory of Brain Functional Genomics (Ministry of Education and Shanghai), School of Life Sciences, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China
Liya Wang
Key Laboratory of Brain Functional Genomics (Ministry of Education and Shanghai), School of Life Sciences, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China
Yi-Hsuan Pan
Key Laboratory of Brain Functional Genomics (Ministry of Education and Shanghai), School of Life Sciences, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China
Xiaohua Cao
Key Laboratory of Brain Functional Genomics (Ministry of Education and Shanghai), School of Life Sciences, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China
Xiaobing Yuan
Key Laboratory of Brain Functional Genomics (Ministry of Education and Shanghai), School of Life Sciences, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China
Thomas Wisniewski
Departments of Neurology, Pathology and Psychiatry, New York University Langone Health, New York, NY, USA
Suying Dang
Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, 227 South Chongqing Road, Shanghai 200025, China; Corresponding author
Wei Zhang
Key Laboratory of Brain Functional Genomics (Ministry of Education and Shanghai), School of Life Sciences, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China; Corresponding author
Summary: Members of a disintegrin and metalloproteinases with thrombospondin motif (ADAMTS) family have been implicated in various vascular diseases. However, their functional roles in early embryonic vascular development are unknown. In this study, we showed that Adamts18 is highly expressed at E11.5-E14.5 in cells surrounding the embryonic aortic arch (AOAR) and the common carotid artery (CCA) during branchial arch artery development in mice. Adamts18 deficiency was found to cause abnormal development of AOAR, CCA, and the third and fourth branchial arch appendages, leading to hypoplastic carotid body, thymus, and variation of middle cerebral artery. Adamts18 was shown to affect the accumulation of extracellular matrix (ECM) components, in particular fibronectin (Fn), around AOAR and CCA. As a result of increased Fn accumulation, the Notch3 signaling pathway was activated to promote the differentiation of cranial neural crest cells (CNCCs) to vascular smooth muscle cells. These data indicate that Adamts18-mediated ECM homeostasis is crucial for the differentiation of CNCCs.
