Integration of IRF6 and Jagged2 signalling is essential for controlling palatal adhesion and fusion competence.
In mammals, adhesion and fusion of the palatal shelves are essential mechanisms during the 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 results 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 the formation and maintenance of the oral periderm, spatio-temporal regulation of which is essential for ensuring appropriate palatal adhesion.
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Rebecca J
RJ
Richardson
Jill
J
Dixon
Rulang
R
Jiang
Michael J
MJ
Dixon
D000818:Animals; D002448:Cell Adhesion; D002972:Cleft Palate / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D000072101:Jagged-2 Protein; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010159:Palate / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism; D015398:Signal Transduction
C528250:IRF6 protein, mouse; D050835:Interferon Regulatory Factors; C490503:Jag2 protein, mouse; D000072101:Jagged-2 Protein; D008565:Membrane Proteins