Adamts18 deficiency in zebrafish embryo causes defective trunk angiogenesis and caudal vein plexus formation
Adamts18 deficiency in zebrafish embryo causes defective trunk angiogenesis and caudal vein plexus formation
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斑马鱼胚胎中 Adamts18 缺陷会导致躯干血管生成和尾静脉丛形成缺陷。
DOI：
10.1016/j.bbrc.2019.10.202
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发表时间：
2020-01-22
影响因子：
3.1
通讯作者：
Zhang, Wei
中科院分区：
文献类型：
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作者：
Lu, Tiantian;Zhang, Tianhao;Zhang, Wei
ADAMTS（具有血小板反应蛋白I型基序的去整合素和金属蛋白酶）酶在各种形态发生过程中起重要作用。为了确定Adamts 18在器官发生早期阶段的功能，我们使用吗啉代反义寡核苷酸（MO）产生外显子3跳跃的adamts 18 mRNA转录本，创建Adamts 18缺陷型斑马鱼。结果表明，Adamts 18缺陷导致斑马鱼胚胎发育缺陷，包括脑室扩大和后脑水肿，眼睛缺陷和尾静脉积血。Adamts 18缺陷还导致主干血管生成受损和尾静脉丛（CVP）的形成。因此，Adamts 18缺陷的斑马鱼胚胎表现出不完全形成的节间血管（ISV），破坏蜂窝状结构的CVP，减少CVP面积和环数。此外，Adamts 18缺乏导致主干、尾静脉（CV）和总主静脉（CCV）的血液循环受损。突变斑马鱼胚胎中的这些异常血管表型被证明与多种血管生成相关信号基因的表达降低相关，包括slit/robo，dll 4/Notch，cox 2和fGFR。这些发现表明Adamts 18在血管网络发育的早期阶段起着关键作用。(C)2019爱思唯尔公司All rights reserved.
ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin type I motifs) enzymes play an important role in various morphogenesis processes. To determine the functions of Adamts18 in the early stages of organogenesis, we created Adamts18 deficient zebrafish using morpholino antisense oligonucleotides (MO) to generate exon 3 skipped adamts18 mRNA transcripts. Results showed that Adamts18 deficiency in zebrafish embryos caused developmental defects, including expanded brain ventricle and hindbrain edema, eye defects, and accumulation of blood in the caudal vein. Adamts18 deficiency also led to impaired trunk angiogenesis and formation of the caudal vein plexus (CVP). Consequently, Adamts18 deficient zebrafish embryos exhibited incomplete formation of intersegment vessels (ISVs), disruption of the honeycomb structure of CVP, and reduced CVP area and loop number. Furthermore, Adamts18 deficiency resulted in impaired blood circulation in major trunk, caudal vein (CV), and common cardinal vein (CCV). These aberrant vascular phenotypes in mutant zebrafish embryos were shown to be associated with a decreased expression of multiple angiogenesis-related signaling genes, including slit/robo, dll4/Notch, cox2, and fgfr. These findings indicate the critical role of Adamts18 in the early stages of vascular network development. (C) 2019 Elsevier Inc. All rights reserved.