Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom.
Champalimaud Centre for the Unknown, Fundação Champalimaud, Lisboa, Portugal.
Dev Biol. 2015 Jan 15;397(2):212-24. doi: 10.1016/j.ydbio.2014.11.007. Epub 2014 Dec 3.
The RAB5 gene family is the best characterised of all human RAB families and is essential for in vitro homotypic fusion of early endosomes. In recent years, the disruption or activation of Rab5 family proteins has been used as a tool to understand growth factor signal transduction in whole animal systems such as Drosophila melanogaster and zebrafish. In this study we have examined the functions for four rab5 genes in zebrafish. Disruption of rab5ab expression by antisense morpholino oligonucleotide (MO) knockdown abolishes nodal signalling in early zebrafish embryos, whereas overexpression of rab5ab mRNA leads to ectopic expression of markers that are normally downstream of nodal signalling. By contrast MO disruption of other zebrafish rab5 genes shows little or no effect on expression of markers of dorsal organiser development. We conclude that rab5ab is essential for nodal signalling and organizer specification in the developing zebrafish embryo.
RAB5 基因家族是所有人类 RAB 家族中研究最透彻的,对于体外早期内体同源融合是必不可少的。近年来,Rab5 家族蛋白的破坏或激活已被用作一种工具,用于研究黑腹果蝇和斑马鱼等整个动物系统中的生长因子信号转导。在这项研究中,我们研究了斑马鱼中四个 rab5 基因的功能。通过反义 morpholino 寡核苷酸(MO)敲低破坏 rab5ab 的表达会使早期斑马鱼胚胎中的 nodal 信号通路失活,而 rab5ab mRNA 的过表达会导致 nodal 信号通路下游的标记物异位表达。相比之下,其他斑马鱼 rab5 基因的 MO 敲低对背器官发育标记物的表达几乎没有影响。我们得出结论,rab5ab 对于发育中的斑马鱼胚胎中的 nodal 信号通路和组织者指定是必不可少的。