Lorén Christina E, Schrader John W, Ahlgren Ulf, Gunhaga Lena
Umeå Center for Molecular Medicine, Building 6M, 4th floor, Umeå University, S-901 87 Umeå, Sweden.
Differentiation. 2009 Apr;77(4):386-94. doi: 10.1016/j.diff.2008.11.003. Epub 2009 Jan 30.
The lens of the eye is derived from the non-neural ectoderm situated next to the optic vesicle. Fibroblast growth factor (FGF) signals play a major role at various stages of vertebrate lens development ranging from induction and proliferation to differentiation. Less is however known about the identity of genes that are induced by FGF activity within the lens. We have isolated and characterized mouse cytoplasmic activation/proliferation-associated protein-2 (Caprin2), with domains belonging to both the Caprin family and the C1q and tumour necrosis factor (TNF) super-family. Here we show that Caprin2 is expressed in the developing vertebrate lens in mouse and chick, and that Caprin2 expression is up-regulated in primary lens fiber cells, after the induction of crystallins the earliest known markers for differentiated lens fiber cells. Caprin2 is subsequently down-regulated in the centre of the lens at the time and at the position of the first fiber cell denucleation and terminal differentiation. In vitro analyses of lens fiber cell differentiation provide evidence that FGF activity emanating from neighboring prospective retinal cells is required and that FGF8 activity is sufficient to induce Caprin2 in lens fiber cells. These results not only provide evidence that FGF signals induce the newly characterized protein Caprin2 in the lens, but also support the general idea that FGF signals are required for lens fiber cell differentiation.
眼睛的晶状体源自紧邻视泡的非神经外胚层。成纤维细胞生长因子(FGF)信号在脊椎动物晶状体发育的各个阶段发挥主要作用,从诱导、增殖到分化。然而,对于晶状体中由FGF活性诱导的基因的身份了解较少。我们分离并鉴定了小鼠细胞质激活/增殖相关蛋白-2(Caprin2),其结构域既属于Caprin家族,也属于C1q和肿瘤坏死因子(TNF)超家族。在此我们表明,Caprin2在小鼠和鸡的发育中的脊椎动物晶状体中表达,并且在晶状体纤维细胞分化的最早已知标志物晶状体蛋白诱导后,Caprin2在初级晶状体纤维细胞中的表达上调。随后,在第一批纤维细胞核去核和终末分化的时间和位置,Caprin2在晶状体中心下调。对晶状体纤维细胞分化的体外分析提供了证据,表明来自相邻预期视网膜细胞的FGF活性是必需的,并且FGF8活性足以在晶状体纤维细胞中诱导Caprin2。这些结果不仅提供了FGF信号在晶状体中诱导新鉴定的蛋白Caprin2的证据,也支持了FGF信号是晶状体纤维细胞分化所必需的这一普遍观点。