Rudkouskaya Alena, Welch Ian, Dagnino Lina
Department of Physiology and Pharmacology, University of Western Ontario, London, ON N6A 5C1, Canada Children's Health Research Institute and Lawson Health Research Institute, University of Western Ontario, London, ON N6A 5C1, Canada.
Mol Biol Cell. 2014 Mar;25(5):620-32. doi: 10.1091/mbc.E13-08-0499. Epub 2013 Dec 26.
Hair follicle morphogenesis requires coordination of multiple signals and communication between its epithelial and mesenchymal constituents. Cell adhesion protein platforms, which include integrins and integrin-linked kinase (ILK), are critical for hair follicle formation. However, their precise contribution to this process is poorly understood. We show that in the absence of ILK, the hair follicle matrix lineage fails to develop, likely due to abnormalities in development of apical-basal cell polarity, as well as in laminin-511 and basement membrane assembly at the tip of the hair bud. These defects also result in impaired specification of hair matrix and absence of precortex and inner sheath root cell lineages. The molecular pathways affected in ILK-deficient follicles are similar to those in the absence of epidermal integrin β1 and include Wnt, but not sonic hedgehog, signaling. ILK-deficient hair buds also show abnormalities in the dermal papilla. Addition of exogenous laminin-511 restores morphological and molecular markers associated with hair matrix formation, indicating that ILK regulates hair bud cell polarity and functions upstream from laminin-511 assembly to regulate the developmental progression of hair follicles beyond the germ stage.
毛囊形态发生需要多种信号的协调以及其上皮和间充质成分之间的通讯。包括整合素和整合素连接激酶（ILK）在内的细胞粘附蛋白平台对毛囊形成至关重要。然而，它们对这一过程的确切贡献尚不清楚。我们发现，在缺乏ILK的情况下，毛囊基质谱系无法发育，这可能是由于顶-基细胞极性发育异常，以及毛芽顶端的层粘连蛋白-511和基底膜组装异常所致。这些缺陷还导致毛囊基质的特化受损，以及前皮质和内根鞘根细胞谱系缺失。ILK缺陷型毛囊中受影响的分子途径与缺乏表皮整合素β1时相似，包括Wnt信号通路，但不包括音猬因子信号通路。ILK缺陷型毛芽在真皮乳头中也表现出异常。添加外源性层粘连蛋白-511可恢复与毛囊基质形成相关的形态和分子标记，表明ILK调节毛芽细胞极性，并在层粘连蛋白-511组装的上游发挥作用，以调节毛囊在胚后阶段的发育进程。
