Desmoglein 4 in hair follicle differentiation and epidermal adhesion: evidence from inherited hypotrichosis and acquired pemphigus vulgaris.
Cell adhesion and communication are interdependent aspects of cell behavior that are critical for morphogenesis and tissue architecture. In the skin, epidermal adhesion is mediated in part by specialized cell-cell junctions known as desmosomes, which are characterized by the presence of desmosomal cadherins, known as desmogleins and desmocollins. We identified a cadherin family member, desmoglein 4, which is expressed in the suprabasal epidermis and hair follicle. The essential role of desmoglein 4 in skin was established by identifying mutations in families with inherited hypotrichosis, as well as in the lanceolate hair mouse. We also show that DSG4 is an autoantigen in pemphigus vulgaris. Characterization of the phenotype of naturally occurring mutant mice revealed disruption of desmosomal adhesion and perturbations in keratinocyte behavior. We provide evidence that desmoglein 4 is a key mediator of keratinocyte cell adhesion in the hair follicle, where it coordinates the transition from proliferation to differentiation.
Kljuic
Ana
A
Department of Genetics and Development, Columbia University, New York, NY 10032, USA.
Bazzi
Hisham
H
Sundberg
John P
JP
Martinez-Mir
Amalia
A
O'Shaughnessy
Ryan
R
Mahoney
My G
MG
Levy
Moise
M
Montagutelli
Xavier
X
Ahmad
Wasim
W
Aita
Vincent M
VM
Gordon
Derek
D
Uitto
Jouni
J
Whiting
David
D
Ott
Jurg
J
Fischer
Stuart
S
Gilliam
T Conrad
TC
Jahoda
Colin A B
CA
Morris
Rebecca J
RJ
Panteleyev
Andrei A
AA
Nguyen
Vu Thuong
VT
Christiano
Angela M
AM
D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004252:DNA Mutational Analysis; D051182:Desmogleins; D004817:Epidermis / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D018859:Hair Follicle / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006983:Hypertrichosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D010392:Pemphigus / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010641:Phenotype
D015820:Cadherins; D003598:Cytoskeletal Proteins; C473409:DSG4 protein, human; D051182:Desmogleins