Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Dag Hammarskjölds väg 20, SE-751 85 Uppsala, Sweden
Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka 565 8565, Japan.
Development. 2019 Jan 25;146(2):dev165589. doi: 10.1242/dev.165589.
Mural cells (MCs) are essential for blood vessel stability and function; however, the mechanisms that regulate MC development remain incompletely understood, in particular those involved in MC specification. Here, we investigated the first steps of MC formation in zebrafish using transgenic reporters. Using and reporters, we show that the onset of expression of , a pericyte marker in adult mice and zebrafish, occurs almost coincidentally with an increment in expression in peri-arterial mesenchymal cells, suggesting that these transcriptional changes mark the specification of MC lineage cells from naïve mesenchymal cells. The emergence of peri-arterial MCs required Notch signaling. We found that -positive cells express in addition to , and although depletion of or failed to block MC emergence, embryos depleted of both and lost mesoderm- as well as neural crest-derived MCs. Using reporters that read out Notch signaling and Notch2 receptor cleavage, we show that Notch activation in the mesenchyme precedes specification into MCs. Taken together, these results show that Notch signaling is necessary for peri-arterial MC specification.
壁细胞（MCs）对于血管的稳定性和功能至关重要；然而，调节 MC 发育的机制仍不完全清楚，特别是涉及 MC 特化的机制。在这里，我们使用转基因报告器研究了斑马鱼中 MC 形成的最初步骤。使用 和 报告器，我们表明，在成年小鼠和斑马鱼中，周细胞标志物 的表达起始几乎与周细胞周围间充质细胞中 的表达增加同时发生，这表明这些转录变化标志着从幼稚的 间充质细胞中特化出 MC 谱系细胞。动脉周围 MCs 的出现需要 Notch 信号。我们发现，除了 之外， -阳性细胞还表达 ，尽管 或 耗竭未能阻止 MC 的出现，但耗竭 两者的胚胎失去了中胚层以及神经嵴衍生的 MCs。使用读取 Notch 信号和 Notch2 受体切割的报告器，我们表明，间充质中的 Notch 激活先于 MC 的特化。综上所述，这些结果表明 Notch 信号对于动脉周围 MC 特化是必需的。
