Jag2-Notch1 signaling regulates oral epithelial differentiation and palate development.
During mammalian palatogenesis, palatal shelves initially grow vertically from the medial sides of the paired maxillary processes flanking the developing tongue and subsequently elevate and fuse with each other above the tongue to form the intact secondary palate. Pathological palate-mandible or palate-tongue fusions have been reported in humans and other mammals, but the molecular and cellular mechanisms that prevent such aberrant adhesions during normal palate development are unknown. We previously reported that mice deficient in Jag2, which encodes a cell surface ligand for the Notch family receptors, have cleft palate associated with palate-tongue fusions. In this report, we show that Jag2 is expressed throughout the oral epithelium and is required for Notch1 activation during oral epithelial differentiation. We show that Notch1 is normally highly activated in the differentiating oral periderm cells covering the developing tongue and the lateral oral surfaces of the mandibular and maxillary processes during palate development. Oral periderm activation of Notch1 is significantly attenuated during palate development in the Jag2 mutants. Further molecular and ultrastructural analyses indicate that oral epithelial organization and periderm differentiation are disrupted in the Jag2 mutants. Moreover, we show that the Jag2 mutant tongue fused to wild-type palatal shelves in recombinant explant cultures. These data indicate that Jag2-Notch1 signaling is spatiotemporally regulated in the oral epithelia during palate development to prevent premature palatal shelf adhesion to other oral tissues and to facilitate normal adhesion between the elevated palatal shelves.
Casey
Liam M
LM
Center for Oral Biology and Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
Lan
Yu
Y
Cho
Eui-Sic
ES
Maltby
Kathleen M
KM
Gridley
Thomas
T
Jiang
Rulang
R
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D005260:Female; D000072101:Jagged-2 Protein; D008297:Male; D008334:Mandible / Q000196:embryology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009061:Mouth Mucosa / Q000196:embryology / Q000378:metabolism; D009154:Mutation; D010159:Palate / Q000196:embryology* / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014059:Tongue / Q000196:embryology / Q000378:metabolism
C490503:Jag2 protein, mouse; D000072101:Jagged-2 Protein; D008565:Membrane Proteins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1