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在鸡胚胎发育过程中,Ptc1和Ptc2转录本提供了Hedgehog信号活性的不同读数。

Ptc1 and Ptc2 transcripts provide distinct readouts of Hedgehog signaling activity during chick embryogenesis.

作者信息

Pearse R V, Vogan K J, Tabin C J

机构信息

Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.

出版信息

Dev Biol. 2001 Nov 1;239(1):15-29. doi: 10.1006/dbio.2001.0430.

Abstract

Hedgehog (Hh) signaling in vertebrates controls patterning and differentiation of a broad range of tissues during development. The Hh receptor Patched (Ptc) is a critical regulator of signaling, maintaining active repression of the pathway in the absence of stimulation, limiting excess diffusion of ligand, and providing an efficient negative feedback mechanism for fine-tuning the responsiveness of receiving cells. Two distinct Ptc genes have been isolated from several vertebrates. Here, we describe the cloning of a second Ptc gene from chick (Ptc2). We show that Ptc1 and Ptc2 are both upregulated at sites of active Hh signaling but that the expression patterns of these genes only partially overlap, thus providing distinct readouts of Hh pathway stimulation. We also show that chick Ptc2 is expressed in the posterior apical ectodermal ridge (AER) of the limb bud in a pattern similar to Fgf4 and that the induction of Ptc2 within the AER, like that of Fgf4, is mediated via antagonism of BMP signaling. The differential responsiveness of cells to Hh pathway stimulation (as marked by the differential induction of Ptc genes) suggests heterogeneity in the mechanisms by which Hh signals are transduced within different populations of receiving cells.

摘要

脊椎动物中的刺猬信号通路(Hh)在发育过程中控制着多种组织的模式形成和分化。Hh受体patched(Ptc)是信号传导的关键调节因子,在没有刺激的情况下维持该通路的活性抑制,限制配体的过度扩散,并提供一种有效的负反馈机制来微调接收细胞的反应性。已经从几种脊椎动物中分离出两个不同的Ptc基因。在这里,我们描述了从鸡中克隆第二个Ptc基因(Ptc2)的过程。我们表明,Ptc1和Ptc2在活跃的Hh信号传导位点均上调,但这些基因的表达模式仅部分重叠,从而提供了Hh信号通路刺激的不同读数。我们还表明,鸡Ptc2在肢芽的后顶端外胚层嵴(AER)中以类似于Fgf4的模式表达,并且AER内Ptc2的诱导,与Fgf4一样,是通过拮抗BMP信号传导介导的。细胞对Hh信号通路刺激的不同反应性(以Ptc基因的差异诱导为标志)表明Hh信号在不同接收细胞群体中传导的机制存在异质性。

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