Metalloprotease-Dependent Onset of Blood Circulation in Zebrafish
Metalloprotease-Dependent Onset of Blood Circulation in Zebrafish
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DOI：
10.1016/j.cub.2010.04.052
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发表时间：
2010-06-22
期刊：
影响因子：
9.2
通讯作者：
Sehara-Fujisawa, Atsuko
中科院分区：
文献类型：
--
作者：
Iida, Atsuo;Sakaguchi, Kazuya;Sehara-Fujisawa, Atsuko
原始血液循环需要血管内血浆流动[1]。然而，目前尚不清楚最早血液循环的开始是否仅取决于功能性循环器官的建立，或者它是否还需要血细胞固有的活跃过程。在这项研究中，我们提出了新的机制，通过监测荧光标记的血液前体和血管在斑马鱼的血液循环的开始。最早的血液循环是同步进行的。这种同步是通过红细胞前体从主动脉下区域侵入后保留在脉管系统的管腔上，然后通过这些前体同时释放到血流中来实现的。形态学和生物化学分析表明，血液循环的开始伴随着血细胞与血管粘附的破坏，需要金属蛋白酶依赖性过程。ADAM8是去整合素和金属蛋白酶（ADAM）家族的成员，介导血液循环的开始。在ADAM8缺失的胚胎中，红系细胞无法从血管腔中分离并停滞。蛋白酶缺陷型ADAM8在红系细胞中的表达导致对血液循环的显性负效应，表明ADAM8的细胞自主作用。基于这些发现，我们提出，第一个红系细胞需要流量依赖的被动和蛋白水解依赖的主动过程进入循环。
The primitive blood circulation requires intravascular plasma flow [1]. However, it remains unclear whether the onset of earliest blood circulation is dependent solely on establishment of a functional circulatory organ or whether it also requires active processes inherent in blood cells. In this study, we present novel mechanisms for the onset of blood circulation by monitoring fluorescently labeled blood precursors and blood vessels in zebrafish. The earliest blood circulation occurs synchronously. This synchrony is achieved by the retention of erythroid precursors on the lumen of the vasculature after their invasion from the subaortic region, and then by simultaneous release of these precursors into the flow. Morphological and biochemical analyses suggest that the onset of blood circulation accompanies disruption of blood cell-to-vessel adhesion and requires metalloprotease-dependent processes. ADAM8, a member of the a disintegrin and metalloprotease (ADAM) family, mediates the onset of blood circulation. In ADAM8-depleted embryos, erythroid cells fail to detach from the vascular lumen and stagnate. Expression of a protease-defective ADAM8 in erythroid cells causes dominant-negative effects on blood circulation, suggesting cell-autonomous roles of ADAM8. Based on these findings, we propose that the first erythroid cells require both flow-dependent passive and proteolysis-dependent active processes to enter the circulation.