Integrating animal models and in vitro tissue models to elucidate the role of desmosomal proteins in diseases.
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.
Department of Dermatology, University of Colorado School of Medicine and Charles C Gates Center for Regenerative Medicine and Stem Cell Biology, University of Colorado School of Medicine , Aurora, CO , USA.
Maranke I
MI
Koster
Jason
J
Dinella
Jiangli
J
Chen
Charlene
C
O'Shea
Peter J
PJ
Koch
D000818:Animals; D002971:Cleft Lip / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002972:Cleft Palate / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051187:Desmocollins / Q000235:genetics / Q000378:metabolism; D051180:Desmoplakins / Q000235:genetics / Q000378:metabolism; D003896:Desmosomes / Q000378:metabolism*; D004476:Ectodermal Dysplasia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005124:Eye Abnormalities / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005143:Eyelids / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008954:Models, Biological; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D051187:Desmocollins; D051180:Desmoplakins; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins