Department of Biochemistry, College of Medicine, Hallym University, ChunCheon, Kangwon-Do, 200-702, Republic of Korea.
Differentiation. 2011 Sep;82(2):99-107. doi: 10.1016/j.diff.2011.05.009.
In early vertebrate development, mesoderm induction is a crucial event regulated by several factors including the activin, BMP and FGF signaling pathways. While the requirement of FGF in Nodal/activin-induced mesoderm formation has been reported, the fate of the tissue modulated by these signals is not fully understood. Here, we examined the fate of tissues when exogenous activin was added and FGF signaling was inhibited in animal cap explants of Xenopus embryos. Activin-induced dorsal mesoderm was converted to ventral mesoderm by inhibition of FGF signaling. We also found that inhibiting FGF signaling in the dorsal marginal zone, in vegetal-animal cap conjugates or in the presence of the activin signaling component Smad2, converted dorsal mesoderm to ventral mesoderm. The expression and promoter activities of a BMP responsive molecule, PV.1 and a Spemann organizer, noggin, were investigated while FGF signaling was inhibited. PV.1 expression increased, while noggin decreased. In addition, inhibiting BMP-4 signaling abolished ventral mesoderm formation induced by exogenous activin and FGF inhibition. Taken together, these results suggest that the formation of dorso-ventral mesoderm in early Xenopus embryos is regulated by a combination of FGF, activin and BMP signaling.
在脊椎动物早期发育过程中,中胚层诱导是由多种因素调节的关键事件,包括激活素、BMP 和 FGF 信号通路。虽然已经报道了 FGF 在 Nodal/激活素诱导的中胚层形成中的需求,但这些信号调节的组织命运还不完全清楚。在这里,我们在非洲爪蟾胚胎的动物帽外植体中研究了添加外源性激活素和抑制 FGF 信号时组织的命运。通过抑制 FGF 信号,激活素诱导的背侧中胚层被转化为腹侧中胚层。我们还发现,抑制背侧边缘区、植物动物帽杂交体或存在激活素信号成分 Smad2 中的 FGF 信号,也可以将背侧中胚层转化为腹侧中胚层。当抑制 FGF 信号时,研究了 BMP 反应分子 PV.1 和 Spemann 组织者 noggin 的表达和启动子活性。PV.1 的表达增加,而 noggin 的表达减少。此外,抑制 BMP-4 信号会消除外源性激活素和 FGF 抑制诱导的腹侧中胚层形成。总之,这些结果表明,早期非洲爪蟾胚胎中背腹中胚层的形成受 FGF、激活素和 BMP 信号的组合调节。