Hanington Patrick C, Patten Shunmoogum A, Reaume Laura M, Waskiewicz Andrew J, Belosevic Miodrag, Ali Declan W
Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
Dev Biol. 2008 Feb 15;314(2):250-60. doi: 10.1016/j.ydbio.2007.10.012. Epub 2007 Oct 22.
Leukemia inhibitory factor (LIF) is a member of the IL-6 cytokine family that functions in the survival, repair and formation of neurons as well as in the maintenance of neural and embryonic stem cells. The functions of LIF have been well documented in mammals, however until recently, the presence of IL-6 family cytokines in ectothermic vertebrates has only been speculated. We report on the identification of lif and lifr transcripts in the zebrafish and document the expression of these molecules in the developing embryos and tissues of adult zebrafish. We also examined the phylogenetic relationship between these molecules and other IL-6 cytokine family members known in mammals. In adult zebrafish, lif is expressed in the kidney and brain while lifr is expressed in the kidney, gill, brain, spleen and liver. During zebrafish embryogenesis, lif and lifr are both expressed as early as 12 hours postfertilization (hpf). In developing zebrafish, lif is expressed in the otic vesicle, retina and cranial sensory ganglia, and lifr is strongly expressed in the notochord, forebrain, otic vesicle, cranial ganglia and the retina. Morpholino knockdown of Lif and Lifr in developing embryos suggests that Lifr, but not Lif is required for proper neural development. lifr morpholino-injected embryos exhibit defects in the trigeminal, facial and vagal branchiomotor neurons, and improper axonal development as measured by acetylated tubulin staining. These embryos also display severe hydrocephaly by 48 hpf. This suggests that Lifrs are involved in proper neural development in zebrafish. This is the first evidence of the expression and role of an LIFR-like molecule in developing fish.
白血病抑制因子（LIF）是白细胞介素-6细胞因子家族的成员，在神经元的存活、修复和形成以及神经和胚胎干细胞的维持中发挥作用。LIF的功能在哺乳动物中已有充分记录，然而直到最近，变温脊椎动物中白细胞介素-6细胞因子家族的存在还只是一种推测。我们报告了斑马鱼中lif和lifr转录本的鉴定，并记录了这些分子在成年斑马鱼发育中的胚胎和组织中的表达。我们还研究了这些分子与哺乳动物中已知的其他白细胞介素-6细胞因子家族成员之间的系统发育关系。在成年斑马鱼中，lif在肾脏和大脑中表达，而lifr在肾脏、鳃、大脑、脾脏和肝脏中表达。在斑马鱼胚胎发育过程中，lif和lifr在受精后12小时（hpf）就开始表达。在发育中的斑马鱼中，lif在耳泡、视网膜和颅感觉神经节中表达，而lifr在脊索、前脑、耳泡、颅神经节和视网膜中强烈表达。在发育中的胚胎中对Lif和Lifr进行吗啉代敲低表明，正常的神经发育需要Lifr而不是Lif。注射了lifr吗啉代的胚胎在三叉神经、面神经和迷走神经鳃运动神经元中表现出缺陷，通过乙酰化微管蛋白染色测量，轴突发育不正常。这些胚胎在48 hpf时还表现出严重的脑积水。这表明Lifrs参与了斑马鱼正常的神经发育。这是LIFR样分子在发育中的鱼类中表达和作用的首个证据。
