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标题：Adamts18 modulates the development of the aortic arch and common carotid artery
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作者：Shuai Ye ; Ning Yang ; Tiantian Lu 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：6
页码：1-18
DOI：10.1016/j.isci.2021.102672
语种：English
出版社：Elsevier
摘要：SummaryMembers 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 thatAdamts18is 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.Graphical abstractDisplay OmittedHighlights•Adamts18is highly expressed during the period of embryonic carotid artery formation•Adamts18 deficiency leads to abnormal AOAR, CCA, MCA branches and carotid appendages•Adamts18 deficiency changes the cerebral infarcted areas in mouse tMCAO model•Adamts18 affects the differentiation of CNCCs to VSMCs by modulating Notch3 pathwayCell biology; Developmental biology;