Gagnon James A, Obbad Kamal, Schier Alexander F
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Development. 2018 Jan 9;145(1):dev147793. doi: 10.1242/dev.147793.
The role of the zebrafish transcription factor Nanog has been controversial. It has been suggested that Nanog is primarily required for the proper formation of the extra-embryonic yolk syncytial layer (YSL) and only indirectly regulates gene expression in embryonic cells. In an alternative scenario, Nanog has been proposed to directly regulate transcription in embryonic cells during zygotic genome activation. To clarify the roles of Nanog, we performed a detailed analysis of zebrafish mutants. Whereas zygotic mutants survive to adulthood, maternal-zygotic (MZ) and maternal mutants exhibit developmental arrest at the blastula stage. In the absence of Nanog, YSL formation and epiboly are abnormal, embryonic tissue detaches from the yolk, and the expression of dozens of YSL and embryonic genes is reduced. Epiboly defects can be rescued by generating chimeric embryos of MZ embryonic tissue with wild-type vegetal tissue that includes the YSL and yolk cell. Notably, cells lacking Nanog readily respond to Nodal signals and when transplanted into wild-type hosts proliferate and contribute to embryonic tissues and adult organs from all germ layers. These results indicate that zebrafish Nanog is necessary for proper YSL development but is not directly required for embryonic cell differentiation.
斑马鱼转录因子Nanog的作用一直存在争议。有人认为，Nanog主要是胚胎外卵黄合胞体层（YSL）正常形成所必需的，并且仅间接调节胚胎细胞中的基因表达。另一种观点认为，Nanog被认为在合子基因组激活期间直接调节胚胎细胞中的转录。为了阐明Nanog的作用，我们对斑马鱼突变体进行了详细分析。虽然合子突变体能够存活至成年，但母源-合子（MZ）和母源突变体在囊胚期表现出发育停滞。在没有Nanog的情况下，YSL的形成和外包异常，胚胎组织与卵黄分离，并且数十种YSL和胚胎基因的表达降低。通过用包含YSL和卵黄细胞的野生型植物组织生成MZ胚胎组织的嵌合胚胎，可以挽救外包缺陷。值得注意的是，缺乏Nanog的细胞很容易对Nodal信号作出反应，并且当移植到野生型宿主中时会增殖并参与来自所有胚层的胚胎组织和成年器官的形成。这些结果表明，斑马鱼Nanog对于YSL的正常发育是必需的，但不是胚胎细胞分化直接所需的。
