Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
J Biol Chem. 2011 Feb 25;286(8):6760-8. doi: 10.1074/jbc.M110.177907. Epub 2010 Dec 21.
Epidermal differentiation in the ventral ectoderm of Xenopus embryos is regulated by the bone morphogenetic protein (BMP) pathway. However, it remains unclear how the BMP pathway is activated and induces the epidermal fate in the ventral ectoderm. Here, we identify a novel player in the BMP pathway that is required for epidermal differentiation during Xenopus early embryonic development. We show that Xenopus EIG121L (xEIG121L) protein, an evolutionarily conserved transmembrane protein, is expressed in the ventral ectoderm at the gastrula and neurula stages. Almost complete knockdown of xEIG121L protein with antisense morpholino oligonucleotides in early Xenopus embryos results in severe developmental defects, including the inhibition of epidermal differentiation and the induction of neural genes. Remarkably, our analysis shows that BMP/Smad1 signaling is severely suppressed in the xEIG121L knockdown ectoderm. Moreover, immunoprecipitation and immunostaining experiments suggest that xEIG121L protein physically interacts, and co-localizes, with BMP receptors. Thus, our results identify a novel regulator of the BMP pathway that has a positive role in BMP signaling and plays an essential role in epidermal differentiation during early embryonic development.
表皮在非洲爪蟾胚胎的腹侧外胚层中的分化受骨形态发生蛋白（BMP）途径的调控。然而，BMP 途径如何被激活并诱导腹侧外胚层中的表皮命运仍然不清楚。在这里，我们鉴定了 BMP 途径中的一种新的调控因子，该因子对于非洲爪蟾早期胚胎发育过程中的表皮分化是必需的。我们发现，一种进化上保守的跨膜蛋白 Xenopus EIG121L（xEIG121L）蛋白在原肠胚和神经胚阶段表达于腹侧外胚层。在早期非洲爪蟾胚胎中用反义 morpholino 寡核苷酸几乎完全敲低 xEIG121L 蛋白会导致严重的发育缺陷，包括表皮分化的抑制和神经基因的诱导。值得注意的是，我们的分析表明，BMP/Smad1 信号在 xEIG121L 敲低的外胚层中受到严重抑制。此外，免疫沉淀和免疫染色实验表明，xEIG121L 蛋白与 BMP 受体发生物理相互作用，并共定位。因此，我们的结果鉴定了 BMP 途径的一种新的调控因子，它在 BMP 信号中具有正向作用，并在早期胚胎发育过程中的表皮分化中发挥重要作用。
