Live imaging of cerebral vascular development in the zebrafish.

脑血管以一种可复制和进化保守的方式形成。人类的初级血管系统由原始颈内动脉(PICA)和原始后脑通道(PHBCs)的一对颅支和尾支发育而来。但这些血管组装并获得其刻板印象的过程仍不清楚。利用转基因斑马鱼的双光子时移成像，我们研究了斑马鱼大脑血管网络的逐步组装和图案化。我们发现CRDIs和Cadis来源于血管母细胞簇的血管生成，血管母细胞簇在12个体节的双侧聚集在视囊的嘴内侧；或者，Picas起源于其他血管母细胞簇，两侧聚集在视囊的尾侧-内侧。吻部和尾部的簇都表达动脉标志物Hey2。PHBCs由15-18个体节的侧腹侧壁后脑的血管母细胞簇两侧发育而来，表达静脉标志物Flt4。我们的结果表明，颅脑血管是由三个主要的血管母细胞簇形成的，这些成血管细胞可能独立于纵向主干轴向血管的血管壁而聚集。

Cranial vessels form in a reproducible and evolutionarily conserved manner. The primary vasculature was considered to develop from a pair of the cranial division (CrDIs) and caudal division (CaDIs) of primitive intercarotid arteries (PICAs) and primordial hindbrain channels (PHBCs) in human. But the process by which these vessels assemble and acquire their stereotypic patterning remains unclear. Using two-photon time-lapse imaging of transgenic zebrafish expressing EGFP predominatly in the endothelial cells including angioblasts, we examine the stepwise assembly and patterning of the vascular network of the zebrafish brain. We show CrDIs and CaDIs originate by angiogenesis from the angioblast clusters, which bilaterally assemble at the rostro-internal to the optic capsule at the stage of 12 somites, and alternatively PICAs develop from the other angioblast clusters, which bilaterally assemble just caudal-internal to the optic capsule. The both rostral and caudal clusters express the arterial maker Hey2. PHBCs develop bilaterally from the clusters of angioblasts arising among the lateral-ventral wall hindbrain at the stages of 15-18 somites, which express the venous maker flt4. Our results suggest that the cranial vessels develop by angiogenesis from the major three clusters of angioblasts, which may assemble independent of the vasuculogeseis of longitudinal trunk axial vessels.