Ault K T, Dirksen M L, Jamrich M
Laboratory of Developmental Biology, Division of Cellular and Gene Therapies, Food and Drug Administration, Rockville, MD 20852-1448, USA.
Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6415-20. doi: 10.1073/pnas.93.13.6415.
The formation of ventral mesoderm has been traditionally viewed as a result of a lack of dorsal signaling and therefore assumed to be a default state of mesodermal development. The discovery that bone morphogenetic protein 4 (BMP4) can induce ventral mesoderm led to the suggestion that the induction of the ventral mesoderm requires a different signaling pathway than the induction of the dorsal mesoderm. However, the individual components of this pathway remained largely unknown. Here we report the identification of a novel Xenopus homeobox gene PV.1 (posterior-ventral 1) that is capable of mediating induction of ventral mesoderm. This gene is activated in blastula stage Xenopus embryos, its expression peaks during gastrulation and declines rapidly after neurulation is complete. PV.1 is expressed in the ventral marginal zone of blastulae and later in the posterior ventral area of gastrulae and neurulae. PV.1 is inducible in uncommited ectoderm by the ventralizing growth factor BMP4 and counteracts the dorsalizing effects of the dominant negative BMP4 receptor. Overexpression of PV.1 yields ventralized tadpoles and rescues embryos partially dorsalized by LiCl treatment. In animal caps, PV.1 ventralizes induction by activin and inhibits expression of dorsal specific genes. All of these effects mimic those previously reported for BMP4. These observations suggest that PV.1 is a critical component in the formation of ventral mesoderm and possibly mediates the effects of BMP4.
传统上，腹侧中胚层的形成被视为缺乏背侧信号的结果，因此被认为是中胚层发育的默认状态。骨形态发生蛋白4（BMP4）可诱导腹侧中胚层这一发现，引发了这样一种观点，即腹侧中胚层的诱导需要一条与背侧中胚层诱导不同的信号通路。然而，该信号通路的具体组成部分在很大程度上仍不清楚。在此，我们报告了一种新的非洲爪蟾同源盒基因PV.1（后腹侧1）的鉴定，它能够介导腹侧中胚层的诱导。该基因在非洲爪蟾囊胚期胚胎中被激活，其表达在原肠胚形成期达到峰值，并在神经胚形成完成后迅速下降。PV.1在囊胚的腹侧边缘区表达，随后在原肠胚和神经胚的后腹侧区域表达。PV.1可被腹侧化生长因子BMP4在未分化的外胚层中诱导表达，并能抵消显性负性BMP4受体的背侧化作用。PV.1的过表达会产生腹侧化的蝌蚪，并拯救因LiCl处理而部分背侧化的胚胎。在动物帽中，PV.1使激活素诱导腹侧化，并抑制背侧特异性基因的表达。所有这些效应都与先前报道的BMP4的效应相似。这些观察结果表明，PV.1是腹侧中胚层形成中的关键成分，可能介导了BMP4的作用。
