Assembly and patterning of the vascular network of the vertebrate hindbrain
Assembly and patterning of the vascular network of the vertebrate hindbrain
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DOI：
10.1242/dev.058776
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发表时间：
2011-05-01
期刊：
影响因子：
4.6
通讯作者：
Weinstein, Brant M.
中科院分区：
文献类型：
--
作者：
Fujita, Misato;Cha, Young R.;Weinstein, Brant M.
颅血管系统对于中枢神经系统的存活和发育是必不可少的，并且在中风和其他脑病理中是重要的。颅血管以可重复和进化保守的方式形成，但这些血管组装和获得其定型模式的过程仍不清楚。在这里，我们研究了斑马鱼后脑血管网络的逐步组装和图案化。在所有脊椎动物中，供应后脑的主要动脉，即基底动脉，沿着后脑的腹侧龙骨。我们发现，这种动脉形式的一个新的过程中，从双边对原始静脉，原始后脑通道的内皮细胞的内侧发芽和迁移。随后，第二波的背芽从原始后脑通道引起血管生成的中央动脉，穿透并支配后脑。趋化因子受体cxcr4a在原始后脑通道的迁移内皮细胞中表达，而其配体cxcl12b在紧邻组装基底动脉的后脑神经龙骨中表达。敲低cxcl12b或cxcr4a会导致基底动脉形成缺陷，表明这一关键动脉的组装和模式依赖于趋化因子信号。
The cranial vasculature is essential for the survival and development of the central nervous system and is important in stroke and other brain pathologies. Cranial vessels form in a reproducible and evolutionarily conserved manner, but the process by which these vessels assemble and acquire their stereotypic patterning remains unclear. Here, we examine the stepwise assembly and patterning of the vascular network of the zebrafish hindbrain. The major artery supplying the hindbrain, the basilar artery, runs along the ventral keel of the hindbrain in all vertebrates. We show that this artery forms by a novel process of medial sprouting and migration of endothelial cells from a bilateral pair of primitive veins, the primordial hindbrain channels. Subsequently, a second wave of dorsal sprouting from the primordial hindbrain channels gives rise to angiogenic central arteries that penetrate into and innervate the hindbrain. The chemokine receptor cxcr4a is expressed in migrating endothelial cells of the primordial hindbrain channels, whereas its ligand cxcl12b is expressed in the hindbrain neural keel immediately adjacent to the assembling basilar artery. Knockdown of either cxcl12b or cxcr4a results in defects in basilar artery formation, showing that the assembly and patterning of this crucial artery depends on chemokine signaling.