Abstract
Desmosomes are intercellular junctions that provide tissues with structural stability. These junctions might also act as signaling centers that transmit environmental clues to the cell, thereby affecting cell differentiation, migration, and proliferation. The importance of desmosomes is underscored by devastating skin and heart diseases caused by mutations in desmosomal genes. Recent observations suggest that abnormal desmosomal protein expression might indirectly contribute to skin disorders previously not linked to these proteins. For example, it has been postulated that reduced desmosomal protein expression occurs in patients affected by Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC), a skin fragility disorder caused by mutations in the transcription factor TP63. Currently, it is not clear how these changes in desmosomal gene expression contribute to AEC. We will discuss new approaches that combine in vitro and in vivo models to elucidate the role of desmosomal gene deregulation in human skin diseases such as AEC.
ACKNOWLEDGMENTS
We would like to thank the University of Colorado School of Medicine Histology Core (www.medschool.ucdenver. edu/histology) and iPSC Core (www.medschool.ucdenver.edu/iPS) for technical support. We would like to thank the National Foundation for Ectodermal Dysplasias (NFED) for providing patient photographs and assistance in obtaining patient skin biopsies.
Declaration of interest: The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
PJK and MIK were supported by a grant from the NFED and by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) under Award Numbers R00 AR054696 (MIK), R01 AR061506 (MIK), and R01 AR053892 (PJK). JD is supported by a pre-doctoral fellowship from the Colorado Clinical & Translational Science Institute (TR001081).