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斑马鱼中的周细胞生物学。

Pericyte Biology in Zebrafish.

机构信息

Department of Biochemistry and Molecular Biology, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada.

出版信息

Adv Exp Med Biol. 2018;1109:33-51. doi: 10.1007/978-3-030-02601-1_4.

Abstract

The zebrafish is an outstanding model for studying vascular biology in vivo. Pericytes and vascular smooth muscle cells can be imaged as they associate with vessels and provide stability and integrity to the vasculature. In zebrafish, pericytes associate with the cerebral and trunk vasculature on the second day of development, as assayed by pdgfrβ and notch3 markers. In the head, cerebral pericytes are neural crest derived, except for the pericytes of the hindbrain vasculature, which are mesoderm derived. Similar to the hindbrain, pericytes on the trunk vasculature are also mesoderm derived. Regardless of their location, pericyte development depends on a complex interaction between blood flow and signalling pathways, such as Notch, SONIC HEDGEHOG and BMP signalling, all of which positively regulate pericyte numbers.Pericyte numbers rapidly increase as development proceeds in order to stabilize both the blood-brain barrier and the vasculature and hence, prevent haemorrhage. Consequently, compromised pericyte development results in compromised vascular integrity, which then evolves into detrimental pathologies. Some of these pathologies have been modelled in zebrafish by inducing mutations in the notch3, foxc1 and foxf2 genes. These zebrafish models provide insights into the mechanisms of disease as associated with pericyte biology. Going forward, these models may be key contributors in elucidating the role of vascular mural cells in regulating vessel diameter and hence, blood flow.

摘要

斑马鱼是研究血管生物学的优秀模型。可以将周细胞和血管平滑肌细胞与血管相关联,为血管提供稳定性和完整性,对其进行成像。在斑马鱼中,通过 pdgfrβ 和 notch3 标记物检测,周细胞在发育的第二天与大脑和躯干血管相关联。在头部,大脑周细胞来源于神经嵴,除了后脑脉管系统的周细胞来源于中胚层。类似于后脑,躯干血管的周细胞也来源于中胚层。无论其位置如何,周细胞的发育都取决于血流和信号通路之间的复杂相互作用,如 Notch、Sonic Hedgehog 和 BMP 信号通路,所有这些通路都积极调节周细胞的数量。随着发育的进行,周细胞的数量迅速增加,以稳定血脑屏障和血管,从而防止出血。因此,周细胞发育受损会导致血管完整性受损,进而发展为有害的病理。通过在 notch3、foxc1 和 foxf2 基因中诱导突变,在斑马鱼中模拟了其中一些病理。这些斑马鱼模型为与周细胞生物学相关的疾病机制提供了深入了解。展望未来,这些模型可能是阐明血管壁细胞在调节血管直径进而调节血流方面的作用的关键贡献者。

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