Titre
Cooperation between the transcription factors p63 and IRF6 is essential to prevent cleft palate in mice.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Thomason, H.A.
Auteure/Auteur
Zhou, H.
Auteure/Auteur
Kouwenhoven, E.N.
Auteure/Auteur
Dotto, G.P.
Auteure/Auteur
Restivo, G.
Auteure/Auteur
Nguyen, B.C.
Auteure/Auteur
Little, H.
Auteure/Auteur
Dixon, M.J.
Auteure/Auteur
van Bokhoven, H.
Auteure/Auteur
Dixon, J.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1558-8238[electronic], 0021-9738[linking]
Statut éditorial
Publié
Date de publication
2010
Volume
120
Numéro
5
Première page
1561
Dernière page/numéro d’article
1569
Peer-reviewed
Oui
Langue
anglais
Résumé
Cleft palate is a common congenital disorder that affects up to 1 in 2,500 live human births and results in considerable morbidity to affected individuals and their families. The etiology of cleft palate is complex, with both genetic and environmental factors implicated. Mutations in the transcription factor-encoding genes p63 and interferon regulatory factor 6 (IRF6) have individually been identified as causes of cleft palate; however, a relationship between the key transcription factors p63 and IRF6 has not been determined. Here, we used both mouse models and human primary keratinocytes from patients with cleft palate to demonstrate that IRF6 and p63 interact epistatically during development of the secondary palate. Mice simultaneously carrying a heterozygous deletion of p63 and the Irf6 knockin mutation R84C, which causes cleft palate in humans, displayed ectodermal abnormalities that led to cleft palate. Furthermore, we showed that p63 transactivated IRF6 by binding to an upstream enhancer element; genetic variation within this enhancer element is associated with increased susceptibility to cleft lip. Our findings therefore identify p63 as a key regulatory molecule during palate development and provide a mechanism for the cooperative role of p63 and IRF6 in orofacial development in mice and humans.
Sujets
PID Serval
serval:BIB_9DED9C317584
PMID
Open Access
Oui
Date de création
2010-09-14T13:38:41.108Z
Date de création dans IRIS
2025-05-20T23:05:46Z