Miyanaga Yuko, Torregroza Ingrid, Evans Todd
Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Mol Cell Biol. 2002 Mar;22(5):1317-28. doi: 10.1128/MCB.22.5.1317-1328.2002.
We identified cDNAs encoding the Xenopus Smad proteins most closely related to mammalian Smad8, and we present a functional analysis of this activity (also referred to recently as xSmad11). Misexpression experiments indicate that xSmad8(11) regulates pathways distinct from those regulated by the closely related xSmad1. Embryos that develop from eggs depleted of xSmad8(11) mRNA fail to gastrulate; instead, at the time of gastrulation, they initiate a widespread program of apoptosis, via a CPP32/caspase 3 pathway. Embryos that avoid this fate display gastrulation defects. Activation of apoptosis is rescued by expression of xSmad8(11) but not xSmad1. Our results demonstrate an embryonic requirement for Smad8(11) activity and show that a maternally derived Smad signaling pathway is required for gastrulation and for mediating a cell survival program during early embryogenesis. We suggest that xSmad8(11) functions as part of a maternally derived mechanism shown previously by others to monitor Xenopus early embryonic cell cycles.
我们鉴定出了编码与哺乳动物Smad8最密切相关的非洲爪蟾Smad蛋白的cDNA，并对该活性（最近也称为xSmad11）进行了功能分析。错误表达实验表明，xSmad8(11)调节的信号通路与密切相关的xSmad1所调节的不同。从耗尽xSmad8(11) mRNA的卵发育而来的胚胎无法进行原肠胚形成；相反，在原肠胚形成时，它们通过CPP32/半胱天冬酶3途径启动广泛的细胞凋亡程序。避免这种命运的胚胎表现出原肠胚形成缺陷。xSmad8(11)的表达可挽救细胞凋亡的激活，但xSmad1则不能。我们的结果证明了胚胎发育对Smad8(11)活性的需求，并表明母源Smad信号通路对于原肠胚形成以及在早期胚胎发育过程中介导细胞存活程序是必需的。我们认为，xSmad8(11)作为一种母源机制的一部分发挥作用，其他人之前已表明该机制可监测非洲爪蟾早期胚胎细胞周期。
