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Desmoglein 4 is regulated by transcription factors implicated in hair shaft differentiation.

Abstract
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.
AuthorsHisham Bazzi, Shadmehr Demehri, Christopher S Potter, Alison G Barber, Alexander Awgulewitsch, Raphael Kopan, Angela M Christiano
JournalDifferentiation; research in biological diversity (Differentiation) Vol. 78 Issue 5 Pg. 292-300 (Dec 2009) ISSN: 1432-0436 [Electronic] England
PMID19683850 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • DSG4 protein, human
  • Desmogleins
  • Dsg4 protein, mouse
  • Dsg4 protein, rat
  • Receptors, Notch
  • Transcription Factors
Topics
  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation
  • Desmogleins (deficiency, metabolism)
  • Gene Expression Regulation
  • Hair (anatomy & histology, metabolism)
  • Humans
  • Mice
  • Mice, Knockout
  • Rats
  • Receptors, Notch (metabolism)
  • Signal Transduction
  • Transcription Factors (metabolism)
  • Transcription, Genetic

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