Latinkić B V, Umbhauer M, Neal K A, Lerchner W, Smith J C, Cunliffe V
Division of Developmental Biology, National Institute for Medical Research (NIMR), The Ridgeway, London NW7 1AA, UK.
Genes Dev. 1997 Dec 1;11(23):3265-76. doi: 10.1101/gad.11.23.3265.
The mesoderm of Xenopus laevis arises through an inductive interaction in which signals from the vegetal hemisphere of the embryo act on overlying equatorial cells. One candidate for an endogenous mesoderm-inducing factor is activin, a member of the TGFbeta superfamily. Activin is of particular interest because it induces different mesodermal cell types in a concentration-dependent manner, suggesting that it acts as a morphogen. These concentration-dependent effects are exemplified by the response of Xbra, expression of which is induced in ectodermal tissue by low concentrations of activin but not by high concentrations. Xbra therefore offers an excellent paradigm for studying the way in which a morphogen gradient is interpreted in vertebrate embryos. In this paper we examine the trancriptional regulation of Xbra2, a pseudoallele of Xbra that shows an identical response to activin. Our results indicate that 381 bp 5' of the Xbra2 transcription start site are sufficient to confer responsiveness both to FGF and, in a concentration-dependent manner, to activin. We present evidence that the suppression of Xbra expression at high concentrations of activin is mediated by paired-type homeobox genes such as goosecoid, Mix.1, and Xotx2.
非洲爪蟾的中胚层通过一种诱导性相互作用产生,在这种相互作用中,胚胎植物半球发出的信号作用于覆盖其上的赤道细胞。一种内源性中胚层诱导因子的候选物是激活素,它是转化生长因子β超家族的成员。激活素特别令人感兴趣,因为它以浓度依赖的方式诱导不同的中胚层细胞类型,这表明它起着形态发生素的作用。这些浓度依赖性效应以Xbra的反应为例,低浓度的激活素能诱导外胚层组织中Xbra的表达,而高浓度则不能。因此,Xbra为研究脊椎动物胚胎中形态发生素梯度的解读方式提供了一个极好的范例。在本文中,我们研究了Xbra2的转录调控,Xbra2是Xbra的一个假等位基因,对激活素表现出相同的反应。我们的结果表明,Xbra2转录起始位点上游381 bp足以赋予对FGF的反应能力,并以浓度依赖的方式赋予对激活素的反应能力。我们提供的证据表明,在高浓度激活素作用下Xbra表达的抑制是由成对型同源框基因介导的,如鹅膏蕈氨酸、Mix.1和Xotx2。