A novel role for Glucocorticoid-Induced TNF Receptor Ligand (Gitrl) in early embryonic zebrafish development.
A novel role for Glucocorticoid-Induced TNF Receptor Ligand (Gitrl) in early embryonic zebrafish development.
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DOI：
10.1387/ijdb.082841lp
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发表时间：
2010
期刊：
影响因子：
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通讯作者：
L. Poulton;K. F. Nolan;C. Anastasaki;H. Waldmann;E. Elizabeth Patton
中科院分区：
文献类型：
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作者：
L. Poulton;K. F. Nolan;C. Anastasaki;H. Waldmann;E. Elizabeth Patton
肿瘤坏死因子配体和受体超家族（TNFSF和TNFRSF）成员在免疫系统中具有多样的和充分研究的功能。此外，一些成员还描述了非免疫学作用，如骨、牙齿、毛发和皮肤的形态发生。GITRL及其受体GITR被充分描述为哺乳动物免疫应答的共调节剂。在这里，我们描述了它们的斑马鱼同源物的鉴定和克隆，并证明了配体（而不是受体）在早期脊椎动物发育中的新作用。同源性和系统发育分析支持斑马鱼Gitrl和Gitr的归属。配体在受精后第一个36小时期间表现出mRNA表达的振荡模式，在此期间未检测到gitr mRNA，并且吗啉代谷胱甘肽介导的gitrl敲低而不是gitr敲低导致早期胚胎发生的破坏，在原肠胚形成期间最清楚地显示，这对应于gitrl mRNA表达的最早峰（5.25-10 hpf）。我们发现Stat 3信号在gitr 1-morphants中被改变，这表明Gitr 1在胚胎发生过程中的一个可能的作用可能是Jak/Stat信号的调节。
Tumour necrosis factor ligand and receptor superfamily (TNFSF and TNFRSF) members have diverse and well-studied functions in the immune system. Additional, non-immunological roles, such as in the morphogenesis of bone, tooth, hair and skin have also been described for some members. GITRL and its receptor GITR are well-described as co-regulators of the mammalian immune response. Here, we describe the identification and cloning of their zebrafish homologues and demonstrate a novel role for the ligand, but not the receptor, in early vertebrate development. The assignment of zebrafish Gitrl and Gitr was supported by homology and phylogenetic analysis. The ligand exhibited an oscillating pattern of mRNA expression during the first 36 hours post fertilization, during which time gitr mRNA was not detected, and morpholino oligonucleotide-mediated knock-down of gitrl, but not of gitr, resulted in disruption of early embryogenesis, most clearly revealed during gastrulation, which corresponded to the earliest peak in gitrl mRNA expression (5.25-10 hpf). We found Stat3 signalling to be altered in the gitrl-morphants, suggesting that one possible role for Gitrl during embryogenesis may be modulation of Jak/Stat signalling.