Abstract：
The normal development of lens fiber cells plays a critical role in lens morphogenesis and maintaining transparency. Factors involved in the development of lens fiber cells are largely unknown in vertebrates. In this study, we reported that GATA2 is essential for lens morphogenesis in Nile tilapia (Oreochromis niloticus). In this study, Gata2a was detected in the primary and secondary lens fiber cells, with the highest expression in primary fiber cells. gata2a homozygous mutants of tilapia were obtained using CRISPR/Cas9. Different from fetal lethality caused by Gata2/gata2a mutation in mice and zebrafish, some gata2a homozygous mutants of tilapia are viable, which provides a good model for studying the role of gata2 in non-hematopoietic organs. Our data showed that gata2a mutation caused extensive degeneration and apoptosis of primary lens fiber cells. The mutants exhibited progressive microphthalmia and blindness in adulthood. Transcriptome analysis of the eyes showed that the expression levels of almost all genes encoding crystallin were significantly down-regulated, while the expression levels of genes involved in visual perception and metal ion binding were significantly up-regulated after gata2a mutation. Altogether, our findings indicate that gata2a is required for the survival of lens fiber cells and provide insights into transcriptional regulation underlying lens morphogenesis in teleost fish.
摘要：
晶状体纤维细胞的正常发育在晶状体形态发生和维持透明度中起着至关重要的作用。在脊椎动物中，与晶状体纤维细胞发育有关的因素在很大程度上是未知的。在这项研究中,我们报道，GATA2对于尼罗罗非鱼（Oreochromisniloticus）的晶状体形态发生至关重要。在这项研究中,Gata2a在初级和次级晶状体纤维细胞中检测到，在原代纤维细胞中表达最高。使用CRISPR/Cas9获得罗非鱼的gata2a纯合突变体。不同于Gata2/gata2a突变对小鼠和斑马鱼的胎儿致死率,罗非鱼的一些gata2a纯合突变体是可行的，为研究gata2在非造血器官中的作用提供了良好的模型。我们的数据表明，gata2a突变导致原代晶状体纤维细胞广泛变性和凋亡。突变体在成年期表现出进行性小眼症和失明。对眼睛的转录组分析表明，几乎所有编码晶状体蛋白的基因的表达水平均显着下调，而gata2a突变后，视觉感知和金属离子结合相关基因的表达水平显著上调。总之,我们的发现表明，gata2a是晶状体纤维细胞存活所必需的，并为硬骨鱼晶状体形态发生的转录调控提供了见解。
