Departments of Genetics & Development, Columbia University, New York, NY 10032, USA.
Differentiation. 2009 Dec;78(5):292-300. doi: 10.1016/j.diff.2009.06.004. Epub 2009 Aug 15.
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 shared. 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.
头发纤维由专门的角蛋白细胞（称为毛母质细胞）组成，这些细胞主要表达角蛋白，这些角蛋白由大量角蛋白相关蛋白（KAP）固定。角蛋白形成毛母质细胞的中间丝细胞骨架，与大量细胞-细胞粘附连接，称为桥粒。桥粒斑蛋白 4（DSG4）是毛干皮质中表达的主要桥粒钙粘蛋白，而角蛋白在毛干皮质中高度表达。在人类中，影响角蛋白或 DSG4 的突变导致具有念珠状毛发表型的毛发，其特征为念珠状毛发。在这项工作中，我们假设调节毛干成分（如角蛋白和 DSG4）表达的调控途径是共享的。因此，我们研究了已知调节角蛋白或 KAP 表达的转录因子/途径对 DSG4 的转录调控。我们表明 HOXC13、LEF1 和 FOXN1 抑制 DSG4 的转录，并提供体外和体内证据表明 Notch 途径与 DSG4 在毛囊中的激活和/或维持相关。
