Division of Molecular Embryology, DKFZ-ZMBH Alliance, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 581, Heidelberg, Germany.
Mech Dev. 2011 Sep-Dec;128(7-10):401-11. doi: 10.1016/j.mod.2011.08.002. Epub 2011 Aug 10.
Gadd45 genes encode a small family of multifunctional stress response proteins, mediating cell proliferation, apoptosis, DNA repair and DNA demethylation. Their role during embryonic development is incompletely understood. Here we identified Xenopus Gadd45b, compared Gadd45a, Gadd45b and Gadd45g expression during Xenopus embryogenesis, and characterized their gain and loss of function phenotypes. Gadd45a and Gadd45g act redundantly and double Morpholino knock down leads to pleiotropic phenotypes, including shortened axes, head defects and misgastrulation. In contrast, Gadd45b, which is expressed at very low levels, shows little effect upon knock down or overexpression. Gadd45ag double Morphants show reduced neural cell proliferation and downregulation of pan-neural and neural crest markers. In contrast, Gadd45ag Morphants display increased expression of multipotency marker genes including Xenopus oct4 homologs as well as gastrula markers, while mesodermal markers are downregulated. The results indicate that Gadd45ag are required for early embryonic cells to exit pluripotency and enter differentiation.
Gadd45 基因编码一小家族多功能应激反应蛋白，介导细胞增殖、凋亡、DNA 修复和 DNA 去甲基化。其在胚胎发育中的作用尚不完全清楚。本研究鉴定了非洲爪蟾 Gadd45b，比较了非洲爪蟾胚胎发育过程中 Gadd45a、Gadd45b 和 Gadd45g 的表达，并对其功能获得和缺失表型进行了表征。Gadd45a 和 Gadd45g 具有冗余作用，双重 Morpholino 敲低导致多种表型，包括轴缩短、头部缺陷和体节错位。相比之下，表达水平极低的 Gadd45b 敲低或过表达几乎没有影响。Gadd45ag 双重 Morphants 显示神经细胞增殖减少和全神经和神经嵴标记物下调。相比之下，Gadd45ag Morphants 显示多能性标记基因的表达增加，包括非洲爪蟾 oct4 同源物以及原肠胚标记物，而中胚层标记物下调。结果表明，Gadd45ag 对于早期胚胎细胞退出多能性并进入分化是必需的。
