Desmoglein 4 is regulated by transcription factors implicated in hair shaft differentiation.
Desmoglein 4 is regulated by transcription factors implicated in hair shaft differentiation.
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DOI：
10.1016/j.diff.2009.06.004
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发表时间：
2009-12
期刊：
影响因子：
2.9
通讯作者：
Christiano, Angela M.
中科院分区：
文献类型：
--
作者：
Bazzi, Hisham;Demehri, Shadmehr;Potter, Christopher S.;Barber, Alison G.;Awgulewitsch, Alexander;Kopan, Raphael;Christiano, Angela M.
毛发纤维由专门的角质形成细胞（称为角质形成细胞）组成，其主要表达由多种角蛋白相关蛋白（KAP）粘合的毛发角蛋白。毛发角蛋白形成毛细胞的中间丝细胞骨架，其连接到丰富的细胞-细胞粘附连接，称为桥粒。桥粒芯糖蛋白4（DSG 4）是在毛干皮质中表达的主要桥粒钙粘蛋白，其中毛角蛋白高度表达。在人类中，影响毛发角蛋白或DSG 4的突变导致具有念珠状发特征的珠状毛发表型。在这项工作中，我们假设，调控毛干成分的表达，如头发角蛋白和DSG 4的调节途径是相似的。因此，我们研究了DSG 4的转录调控的转录因子/途径，已知的头发角蛋白或KAP表达的调节器。我们发现HOXC 13，LEF 1和FOXN 1抑制DSG 4转录，并提供了在体外和体内证据相关的Notch途径与激活和/或维持DSG 4在毛囊中的表达。
The hair fiber is made of specialized keratinocytes, known as trichocytes, that primarily express hair keratins which are cemented by a multitude of keratin-associated proteins (KAPs). The hair keratins form the intermediate filament cytoskeleton of the trichocytes, which are linked to abundant cell-cell adhesion junctions, called desmosomes. Desmoglein 4 (DSG4) is the major desmosomal cadherin expressed in the hair shaft cortex where the hair keratins are highly expressed. In humans, mutations affecting either the hair keratins or DSG4 lead to beaded hair phenotypes with features of monilethrix. In this work, we postulated that the regulatory pathways governing the expression of hair shaft components, such as hair keratins and DSG4, are similar. Therefore, we studied the transcriptional regulation of DSG4 by transcription factors/pathways that are known regulators of hair keratin or KAP expression. We show that HOXC13, LEF1 and FOXN1 repress DSG4 transcription and provide in vitro and in vivo evidence correlating the Notch pathway with the activation and/or maintenance of DSG4 expression in the hair follicle.
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