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PLoS Genet. 2017 Jun 12;13(6):e1006828. doi: 10.1371/journal.pgen.1006828. eCollection 2017 Jun.

p63 exerts spatio-temporal control of palatal epithelial cell fate to prevent cleft palate.

Author information

1
Faculty of Biology, Medicine & Health, Manchester Academic Health Sciences Centre, Michael Smith Building, University of Manchester, Manchester, United Kingdom.
2
CEINGE Biotecnologie Avanzate Scarl (Center for Genetic Engineering), Napoli, Italy.
3
Department of Molecular Developmental Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands.
4
Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands.
5
Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
6
Department of Biology, University of Naples, Federico II, Napoli, Italy.
7
Department of Oral Biology, School of Dental Medicine, State University of New York at Buffalo, Buffalo, New York, United States of America.
8
Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, United States of America.

Abstract

Cleft palate is a common congenital disorder that affects up to 1 in 2500 live births and results in considerable morbidity to affected individuals and their families. The aetiology of cleft palate is complex with both genetic and environmental factors implicated. Mutations in the transcription factor p63 are one of the major individual causes of cleft palate; however, the gene regulatory networks in which p63 functions remain only partially characterized. Our findings demonstrate that p63 functions as an essential regulatory molecule in the spatio-temporal control of palatal epithelial cell fate to ensure appropriate fusion of the palatal shelves. Initially, p63 induces periderm formation and controls its subsequent maintenance to prevent premature adhesion between adhesion-competent, intra-oral epithelia. Subsequently, TGFβ3-induced down-regulation of p63 in the medial edge epithelia of the palatal shelves is a pre-requisite for palatal fusion by facilitating periderm migration from, and reducing the proliferative potential of, the midline epithelial seam thereby preventing cleft palate.

PMID:
28604778
PMCID:
PMC5484519
DOI:
10.1371/journal.pgen.1006828
[Indexed for MEDLINE]
Free PMC Article

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