Conserved and context-dependent roles for Pdgfrb signaling during zebrafish vascular mural cell development
Conserved and context-dependent roles for Pdgfrb signaling during zebrafish vascular mural cell development
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DOI：
10.1101/2021.03.29.437552
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发表时间：
2021-03
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影响因子：
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通讯作者：
Koji Ando;Yu-Huan Shih;Lwaki Ebarasi;A. Grosse;Daneal Portman;Ayano Chiba;K. Mattonet;C. Gerri
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文献类型：
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作者：
Koji Ando;Yu-Huan Shih;Lwaki Ebarasi;A. Grosse;Daneal Portman;Ayano Chiba;K. Mattonet;C. Gerri
血小板衍生生长因子β及其受体PDGFRb在包括周细胞和血管平滑肌在内的血管壁细胞的发育中起重要作用。为了确定这个角色在斑马鱼中是否保守，我们分析了pdgfb和PDGFRb突变系。与小鼠相似，pdgfb和pdGFRb突变体斑马鱼缺乏脑周细胞，并表现出解剖学上选择性地丧失血管平滑肌覆盖。尽管有这些缺陷，PDGFRb突变斑马鱼在幼体阶段没有表现出循环缺陷。然而，从幼年期开始，我们观察到在PDGFRb突变体中，严重的颅脑出血和血管扩张与周细胞和血管平滑肌细胞的丢失相关。与小鼠类似，PDGFRb突变斑马鱼也显示出肾小球结构缺陷，但肝星状细胞发育正常。我们还注意到冠状动脉上有缺陷的壁细胞投资伴随着发育过程中的缺陷。总之，我们的研究支持壁细胞中PDGFRb信号的保守要求。此外，这些突变体为明确研究早期胚胎阶段的壁细胞提供了一个重要的模型，而不会混淆循环缺陷的次要影响。对斑马鱼的遗传分析表明，在脊椎动物的血管发育过程中，Pdgfb/PDGFRb信号在周细胞和血管平滑肌细胞的形成中具有保守的作用。
Platelet derived growth factor beta and its receptor, Pdgfrb, play essential roles in the development of vascular mural cells, including pericytes and vascular smooth muscle. To determine if this role was conserved in zebrafish, we analyzed pdgfb and pdgfrb mutant lines. Similar to mouse, pdgfb and pdgfrb mutant zebrafish lack brain pericytes and exhibit anatomically selective loss of vascular smooth muscle coverage. Despite these defects, pdgfrb mutant zebrafish did not otherwise exhibit circulatory defects at larval stages. However, beginning at juvenile stages, we observed severe cranial hemorrhage and vessel dilation associated with loss of pericytes and vascular smooth muscle cells in pdgfrb mutants. Similar to mouse, pdgfrb mutant zebrafish also displayed structural defects in the glomerulus, but normal development of hepatic stellate cells. We also noted defective mural cell investment on coronary vessels with concomitant defects in their development. Together, our studies support a conserved requirement for Pdgfrb signaling in mural cells. In addition, these mutants provide an important model for definitive investigation of mural cells during early embryonic stages without confounding secondary effects from circulatory defects. Summary statement Genetic analysis in zebrafish demonstrates the conserved role of Pdgfb/Pdgfrb signaling in pericyte and vascular smooth muscle cell formation during vascular development in vertebrates.