Gritli-Linde Amel, Hallberg Kristina, Harfe Brian D, Reyahi Azadeh, Kannius-Janson Marie, Nilsson Jeanette, Cobourne Martyn T, Sharpe Paul T, McMahon Andrew P, Linde Anders
Department of Oral Biochemistry, Sahlgrenska Academy at Göteborg University, Medicinaregatan 12F, Göteborg, Sweden.
Dev Cell. 2007 Jan;12(1):99-112. doi: 10.1016/j.devcel.2006.12.006.
We show that removing the Shh signal tranducer Smoothened from skin epithelium secondarily results in excess Shh levels in the mesenchyme. Moreover, the phenotypes we observe reflect decreased epithelial Shh signaling, yet increased mesenchymal Shh signaling. For example, the latter contributes to exuberant hair follicle (HF) induction, while the former depletes the resulting follicular stem cell niches. This disruption of the niche apparently also allows the remaining stem cells to initiate hair formation at inappropriate times. Thus, the temporal structure of the hair cycle may depend on the physical structure of the niche. Finally, we find that the ablation of epithelial Shh signaling results in unexpected transformations: the follicular outer root sheath takes on an epidermal character, and certain HFs disappear altogether, having adopted a strikingly mammary gland-like fate. Overall, our study uncovers a multifaceted function for Shh in sculpting and maintaining the integrity and identity of the developing HF.
我们发现，从皮肤上皮细胞中去除Shh信号转导蛋白Smo后，间充质中会继发产生过量的Shh水平。此外，我们观察到的表型反映出上皮细胞中Shh信号传导减少，而间充质中Shh信号传导增加。例如，后者导致毛囊（HF）过度诱导，而前者则耗尽了由此产生的毛囊干细胞微环境。这种微环境的破坏显然也使得剩余的干细胞在不适当的时间启动毛发形成。因此，毛发周期的时间结构可能取决于微环境的物理结构。最后，我们发现上皮细胞Shh信号传导的缺失会导致意想不到的转变：毛囊外根鞘呈现出表皮特征，某些毛囊完全消失，呈现出惊人的乳腺样命运。总体而言，我们的研究揭示了Shh在塑造和维持发育中的毛囊的完整性和特性方面具有多方面的功能。
