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首页> 外文期刊>Development >Ectodysplasin has a dual role in ectodermal organogenesis: inhibition of Bmp activity and induction of Shh expression.
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Ectodysplasin has a dual role in ectodermal organogenesis: inhibition of Bmp activity and induction of Shh expression.

机译：蜕皮素在外胚层器官发生中具有双重作用：抑制Bmp活性和诱导Shh表达。

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Ectodermal organogenesis is regulated by inductive and reciprocal signalling cascades that involve multiple signal molecules in several conserved families. Ectodysplasin-A (Eda), a tumour necrosis factor-like signalling molecule, and its receptor Edar are required for the development of a number of ectodermal organs in vertebrates. In mice, lack of Eda leads to failure in primary hair placode formation and missing or abnormally shaped teeth, whereas mice overexpressing Eda are characterized by enlarged hair placodes and supernumerary teeth and mammary glands. Here, we report two signalling outcomes of the Eda pathway: suppression of bone morphogenetic protein (Bmp) activity and upregulation of sonic hedgehog (Shh) signalling. Recombinant Eda counteracted Bmp4 activity in developing teeth and, importantly, inhibition of BMP activity by exogenous noggin partially restored primary hair placode formation in Eda-deficient skin in vitro, indicating that suppression of Bmp activity was compromised in the absence of Eda. The downstream effects of the Eda pathway are likely to be mediated by transcription factor nuclear factor-kappaB (NF-kappaB), but the transcriptional targets of Edar have remained unknown. Using a quantitative approach, we show in cultured embryonic skin that Eda induced the expression of two Bmp inhibitors, Ccn2/Ctgf (CCN family protein 2/connective tissue growth factor) and follistatin. Moreover, our data indicate that Shh is a likely transcriptional target of Edar, but, unlike noggin, recombinant Shh was unable to rescue primary hair placode formation in Eda-deficient skin explants.
机译：外胚层器官发生受涉及多个保守家族中的多个信号分子的诱导性和交互性信号级联的调节。 Ectodysplasin-A（Eda）（一种肿瘤坏死因子样信号分子）及其受体Edar是脊椎动物中许多外胚层器官发育所必需的。在小鼠中，缺乏Eda会导致初级毛发斑块形成失败以及牙齿缺失或畸形，而过度表达Eda的小鼠的特征是头发斑块增大，多余的牙齿和乳腺。在这里，我们报告Eda途径的两个信号转导结果：抑制骨形态发生蛋白（Bmp）活性和上调刺猬（Shh）信号转导。重组Eda抵消了发育中的牙齿中的Bmp4活性，重要的是，外源性Noggin抑制BMP活性可部分恢复体外Eda缺乏皮肤中初级发斑的形成，这表明在缺乏Eda的情况下，对Bmp活性的抑制会受到损害。 Eda途径的下游效应可能是由转录因子核因子-κB（NF-kappaB）介导的，但Edar的转录靶点仍然未知。使用定量方法，我们在培养的胚胎皮肤中显示Eda诱导了两种Bmp抑制剂Ccn2 / Ctgf（CCN家族蛋白2 /结缔组织生长因子）和卵泡抑素的表达。此外，我们的数据表明，Shh可能是Edar的转录靶标，但与noggin不同，重组Shh无法挽救Eda缺陷型皮肤外植体中主要发斑的形成。

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