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Human Molecular Genetics Advance Access published online on May 13, 2009
Human Molecular Genetics, doi:10.1093/hmg/ddp201
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© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Integration of IRF6 and Jagged2 signalling is essential for controlling palatal adhesion and fusion competence

Rebecca J. Richardson1, Jill Dixon1, Rulang Jiang2 and Michael J. Dixon1,*

1 Faculty of Life Sciences and Dental School, University of Manchester, Oxford Road, Manchester. M13 9PT. UK 2 Center for Oral Biology and Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, New York

* Corresponding author: Professor Michael Dixon, Faculty of Life Sciences, Michael Smith Building, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom, E-mail: mike.dixon{at}manchester.ac.uk, Telephone: +44 (0)161-275 5620, Fax: +44 (0) 161-275 5082

Received December 16, 2008; Revised April 28, 2009; Accepted April 28, 2009

In mammals, adhesion and fusion of the palatal shelves are essential mechanisms during development of the secondary palate; failure of these processes leads to the congenital anomaly, cleft palate. The mechanisms that prevent pathological adhesion between the oral and palatal epithelia while permitting adhesion and subsequent fusion of the palatal shelves via their medial edge epithelia remain obscure. In humans, mutations in the transcription factor interferon regulatory factor 6 (IRF6) underlie Van der Woude syndrome and popliteal pterygium syndrome. Recently, we have demonstrated that mice homozygous for a mutation in Irf6 exhibit abnormalities of epithelial differentiation that result in cleft palate as a consequence of adhesion between the palatal shelves and the tongue. In the current paper, we demonstrate that Irf6 is essential for oral epithelial differentiation and that IRF6 and the Notch ligand Jagged2 function in convergent molecular pathways during this process. We further demonstrate that IRF6 plays a key role in formation and maintenance of the oral periderm, spatio-temporal regulation of which is essential for ensuring appropriate palatal adhesion.


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