Essential role for Sonic hedgehog during hair follicle morphogenesis
Essential role for Sonic hedgehog during hair follicle morphogenesis
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DOI：
10.1006/dbio.1998.9103
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发表时间：
1999-01-01
影响因子：
2.7
通讯作者：
Dlugosz, AA
中科院分区：
文献类型：
--
作者：
Chiang, C;Swan, RZ;Dlugosz, AA
毛囊是上皮干细胞的来源，也是几种皮肤肿瘤的起源部位。尽管很明显毛囊是通过一系列诱导性组织相互作用产生的，但识别驱动这一过程的信号分子仍然是皮肤生物学中的一个重大挑战。在这项研究中，我们报道了分泌型形态发生素音猬因子（Shh）在毛囊发育过程中的关键作用。在对照胚胎和Shh -/-胚胎中都检测到了由表皮基板和相关真皮凝聚物组成的毛芽，但在突变体皮肤中，毛囊发育后续阶段的进展受阻。Gli1和Ptc1在Shh -/-真皮凝聚物中的表达降低，并且它们未能发育成毛囊乳头，这表明相邻的间充质是基板衍生的Shh的关键靶标。尽管毛囊形态发生受到严重抑制，但在Shh -/-皮肤移植物以及用环巴胺处理以阻断Shh信号的培养触须外植体中都检测到了晚期毛囊分化标志物。我们的研究结果揭示了Shh在毛囊形态发生过程中的重要作用，它是发育超越毛芽阶段正常进展所必需的。（C）1999年学术出版社。
The hair follicle is a source of epithelial stem cells and site of origin for several types of skin tumors. Although it is clear that follicles arise by way of a series of inductive tissue interactions, identification of the signaling molecules driving this process remains a major challenge in skin biology. In this study we report an obligatory role for the secreted morphogen Sonic hedgehog (Shh) during hair follicle development. Hair germs comprising epidermal placodes and associated dermal condensates were detected in both control and Shh -/- embryos, but progression through subsequent stages of follicle development was blocked in mutant skin. The expression of Gli1 and Ptc1 was reduced in Shh -/- dermal condensates and they failed to evolve into hair follicle papillae, suggesting that the adjacent mesenchyme is a critical target for placode-derived Shh. Despite the profound inhibition of hair follicle morphogenesis, late-stage follicle differentiation markers were detected in Shh -/- skin grafts, as well as cultured vibrissa explants treated with cyclopamine to block Shh signaling. Our findings reveal an essential role for Shh during hair follicle morphogenesis, where it is required for normal advancement beyond the hair germ stage of development. (C) 1999 Academic Press.