Laminin-10 is crucial for hair morphogenesis
Laminin-10 is crucial for hair morphogenesis
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DOI：
10.1093/emboj/cdg239
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发表时间：
2003-05-15
期刊：
影响因子：
11.4
通讯作者：
Marinkovich, MP
中科院分区：
文献类型：
--
作者：
Li, J;Tzu, J;Marinkovich, MP
细胞外基质在皮肤形态发生中的作用尚不清楚。在这里，我们描述了层粘连蛋白 10 (alpha5beta1gamma1) 在毛囊发育中的重要作用。当其他层粘连蛋白下调时，层粘连蛋白 10 存在于伸长毛发胚芽的基底膜中，这表明层粘连蛋白 10 在头发发育中发挥作用。用层粘连蛋白 10 或其受体 β1 整合素的抗体治疗人类头皮异种移植物会产生脱发。 E16.5 Lama5 -/- 小鼠皮肤缺乏层粘连蛋白-10，与对照相比含有较少的毛胚，移植后，Lama5 -/- 皮肤显示毛胚伸长失败，随后毛囊完全退化。 Lama5 -/- 皮肤显示基底膜组装有缺陷，失巢凋亡没有明显增加。相反，Lama5 -/- 皮肤显示出早期毛发标记物（包括 sonic hedgehog 和 Gli1）的表达减少，这表明层粘连蛋白 10 在发育信号传导中发挥着重要作用。有趣的是，用纯化的层粘连蛋白10处理Lama5 -/- 皮肤可以纠正基底膜缺陷并恢复毛囊发育。我们得出结论，层粘连蛋白 10 是毛囊发育所必需的，并报告了首次使用外源蛋白来纠正皮肤发育缺陷。
The role of the extracellular matrix in cutaneous morphogenesis is poorly understood. Here, we describe the essential role of laminin-10 (alpha5beta1gamma1) in hair follicle development. Laminin-10 was present in the basement membrane of elongating hair germs, when other laminins were downregulated, suggesting a role for laminin-10 in hair development. Treatment of human scalp xenografts with antibodies to laminin-10, or its receptor beta1 integrin, produced alopecia. E16.5 Lama5 -/- mouse skin, lacking laminin-10, contained fewer hair germs compared with controls, and after transplantation, Lama5 -/- skin showed a failure of hair germ elongation followed by complete hair follicle regression. Lama5 -/- skin showed defective basement membrane assembly, without measurable increases in anoikis. Instead, Lama5 -/- skin showed decreased expression of early hair markers including sonic hedgehog and Gli1, implicating laminin-10 in developmental signaling. Intriguingly, treatment of Lama5 -/- skin with purified laminin-10 corrected basement membrane defects and restored hair follicle development. We conclude that laminin-10 is required for hair follicle development and report the first use of exogenous protein to correct a cutaneous developmental defect.