Neurovascular development in the embryonic zebrafish hindbrain.
Neurovascular development in the embryonic zebrafish hindbrain.
复制标题
DOI：
10.1016/j.ydbio.2011.06.037
复制
发表时间：
2011-09
影响因子：
2.7
通讯作者：
F. Ulrich;Leung-hang Ma;R. Baker;Jesús Torres-Vázquez
中科院分区：
文献类型：
--
作者：
F. Ulrich;Leung-hang Ma;R. Baker;Jesús Torres-Vázquez
大脑由数十亿个高度代谢活跃的神经元组成，这些神经元的活动为认知、情感、感觉和运动功能提供了基础。脑血管系统通过为大脑提供所有器官中最大的血液供应来满足大脑对氧气和葡萄糖的异常高需求。因此，脑血管疾病，如先天性血管畸形、中风和肿瘤，会损害神经元功能和存活，并常常造成致残或致命的后果。然而，脑血管系统的组装是一个仍然知之甚少的过程。在这里，我们利用斑马鱼胚胎的物理和光学可及性来表征胚胎后脑内的脑血管发育。我们发现这个过程主要是由内皮细胞迁移驱动的，并遵循两个步骤的顺序。首先，沿神经外胚层腹外侧表面形成具有典型解剖结构的神经周围血管。其次，来自神经周围血管子集的血管新生芽迁移到后脑形成神经内血管系统。我们发现这些血管生成芽通过菱形球中心可再生地渗透到后脑，那里有分化的神经元存在，并且特定的菱形球总是首先血管化。虽然神经内血管的解剖结构因动物而异，但神经周围血管和神经内血管连接的某些方面在特定的后脑区域可重复发生。使用VEGF信号的化学抑制剂，我们确定了该途径在后脑血管形成过程中的阶段特异性需求。最后，我们发现后脑血管的一个子集与典型的神经元簇和轴突束排列或非常接近。利用内皮缺乏的时钟突变体，我们发现内皮对于后脑早期这些典型的神经元簇和轴突束的组织和维持是必不可少的。然而，小脑的上菱形唇和视顶盖在clo中是异常的。总的来说，这项研究提供了详细的、多阶段的早期斑马鱼后脑神经血管发育的细胞分辨率，直到第三天的年龄。因此，这项工作为突变体、变形体和药物处理胚胎的神经血管特征提供了有用的参考。
The brain is made of billions of highly metabolically active neurons whose activities provide the seat for cognitive, affective, sensory and motor functions. The cerebral vasculature meets the brain's unusually high demand for oxygen and glucose by providing it with the largest blood supply of any organ. Accordingly, disorders of the cerebral vasculature, such as congenital vascular malformations, stroke and tumors, compromise neuronal function and survival and often have crippling or fatal consequences. Yet, the assembly of the cerebral vasculature is a process that remains poorly understood. Here we exploit the physical and optical accessibility of the zebrafish embryo to characterize cerebral vascular development within the embryonic hindbrain. We find that this process is primarily driven by endothelial cell migration and follows a two-step sequence. First, perineural vessels with stereotypical anatomies are formed along the ventro-lateral surface of the neuroectoderm. Second, angiogenic sprouts derived from a subset of perineural vessels migrate into the hindbrain to form the intraneural vasculature. We find that these angiogenic sprouts reproducibly penetrate into the hindbrain via the rhombomere centers, where differentiated neurons reside, and that specific rhombomeres are invariably vascularized first. While the anatomy of intraneural vessels is variable from animal to animal, some aspects of the connectivity of perineural and intraneural vessels occur reproducibly within particular hindbrain locales. Using a chemical inhibitor of VEGF signaling we determine stage-specific requirements for this pathway in the formation of the hindbrain vasculature. Finally, we show that a subset of hindbrain vessels is aligned and/or in very close proximity to stereotypical neuron clusters and axon tracts. Using endothelium-deficient cloche mutants we show that the endothelium is dispensable for the organization and maintenance of these stereotypical neuron clusters and axon tracts in the early hindbrain. However, the cerebellum's upper rhombic lip and the optic tectum are abnormal in clo. Overall, this study provides a detailed, multi-stage characterization of early zebrafish hindbrain neurovascular development with cellular resolution up to the third day of age. This work thus serves as a useful reference for the neurovascular characterization of mutants, morphants and drug-treated embryos.