Analysis of Meox-2 mutant mice reveals a novel postfusion-based cleft palate.
Cleft palate represents a common human congential disease involving defects in the development of the secondary palate. Major steps in mammalian palatogenesis include vertical growth, elevation, and fusion of the palate shelves. Our current study with the homeobox gene Meox-2 during mouse secondary palate development reveals a novel postfusion-based mechanism for cleft palate. Meox-1 and Meox-2 are two functionally related homeobox genes playing important roles in somitogenesis and limb muscle differentiation. We found that the expression of Meox-2, not Meox-1, marks the specification of early mouse palatal mesenchymal cells in the maxillary processes at embryonic day 11.5 (E11.5). From E12.5 to E15.5, the expression of Meox-2 occupies only the posterior part of the palate, providing an early molecular marker for the anterior-posterior polarity in mouse secondary palate formation. A total of 35.3% of Meox-2-/- (n = 17) and 25.5% of Meox-2+/- (n = 55) mouse embryos display a cleft palate phenotype at E15.5, indicating that the reduction of Meox-2 function is associated with susceptibility to cleft palate. Unlike previously reported clefts, none of the clefts found in Meox-2 mutants contain any epithelial sheets in the medial edge areas, and detailed examination revealed that the clefts resulted from the breakdown of newly fused palates. This article is the first report of a gene required to maintain adherence of the palatal shelves after fusion.
Jin
Jiu-Zhen
JZ
Department of Molecular, Cellular & Craniofacial Biology and Birth Defects Center, University of Louisville, Louisville, Kentucky 40292, USA.
Ding
Jixiang
J
D000818:Animals; D002972:Cleft Palate / Q000196:embryology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D051956:Goosecoid Protein / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009924:Organ Culture Techniques; D010641:Phenotype
D051956:Goosecoid Protein; C497993:Gsc protein, mouse; D018398:Homeodomain Proteins; C484194:Meox2 protein, mouse