NF-κB transmits Eda A1/EdaR signalling to activate Shh and cyclin D1 expression, and controls post-initiation hair placode down growth
NF-κB transmits Eda A1/EdaR signalling to activate Shh and cyclin D1 expression, and controls post-initiation hair placode down growth
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DOI：
10.1242/dev.02278
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发表时间：
2006-03-15
期刊：
影响因子：
4.6
通讯作者：
Scheidereit, C
中科院分区：
文献类型：
--
作者：
Schmidt-Ullrich, R;Tobin, DJ;Scheidereit, C
在一个NF - κB活性受抑制（c(IκBαΔN)）的小鼠模型中，发现了NF - κB在大多数外胚层附属物（包括两种类型的小鼠皮毛毛囊）发育中的一种新功能。然而，NF - κB在毛囊中所调控的发育过程仍然未知。此外，c(IκBαΔN)小鼠的表型与Eda A1（斑猫）或其受体EdaR（无毛）缺陷小鼠的表型相似，这引发了体内NF - κB是调控这些新型肿瘤坏死因子家族成员，还是被它们调控的问题。我们现在证明，表皮NF - κB活性在胚胎第14.5天首先在初级针毛毛囊的基板中被观察到，并且体内NF - κB信号在Eda A1和EdaR的下游被激活。重要的是，激活NF - κB的异位信号也能刺激针毛基板的形成，这表明NF - κB在基板发育中起关键作用。在无毛和c(IκBαΔN)小鼠中，基板开始发育，但在缺乏EdaR/NF - κB信号的情况下迅速夭折。我们表明NF - κB的激活对于诱导Shh和细胞周期蛋白D1的表达以及随后的基板向下生长是必不可少的。然而，细胞周期蛋白D1的诱导似乎是由NF - κB间接调控的，可能是通过Shh和Wnt。与斑猫小鼠相比，在c(IκBαΔN)小鼠中观察到的毛囊数量大幅减少，这表明其他信号，如TROY，必须调控特定毛囊亚型中的NF - κB活性。
A novel function of NF-kappa B in the development of most ectodermal appendages, including two types of murine pelage hair follicles, was detected in a mouse model with suppressed NF-kappa B activity (c(I kappa B alpha Delta N)). However, the developmental processes regulated by NF-kappa B in hair follicles has remained unknown. Furthermore, the similarity between the phenotypes of c(I kappa BA Delta N) mice and mice deficient in Eda A1 (tabby) or its receptor EdaR (downless) raised the issue of whether in vivo NF-kappa B regulates or is regulated by these novel TNF family members. We now demonstrate that epidermal NF-kappa B activity is first observed in placodes of primary guard hair follicles at day E14.5, and that in vivo NF-kappa B signalling is activated downstream of Eda A1 and EdaR. Importantly, ectopic signals which activate NF-kappa B can also stimulate guard hair placode formation, suggesting a crucial role for NF-kappa B in placode development. In downless and c(I kappa B alpha Delta N) mice, placodes start to develop, but rapidly abort in the absence of EdaR/NF-kappa B signalling. We show that NF-kappa B activation is essential for induction of Shh and cyclin D1 expression and subsequent placode down growth. However, cyclin D1 induction appears to be indirectly regulated by NF-kappa B, probably via Shh and Wnt. The strongly decreased number of hair follicles observed in c(I kappa B alpha Delta N) mice compared with tabby mice, indicates that additional signals, such as TROY, must regulate NF-kappa B activity in specific hair follicle subtypes.