title: Pax9 regulates a molecular network involving Bmp4, Fgf10, Shh signaling and the Osr2 transcription factor to control palate morphogenesis.
abstract: Cleft palate is one of the most common birth defects in humans. Whereas gene knockout studies in mice have shown that both the Osr2 and Pax9 transcription factors are essential regulators of palatogenesis, little is known about the molecular mechanisms involving these transcription factors in palate development. We report here that Pax9 plays a crucial role in patterning the anterior-posterior axis and outgrowth of the developing palatal shelves. We found that tissue-specific deletion of Pax9 in the palatal mesenchyme affected Shh expression in palatal epithelial cells, indicating that Pax9 plays a crucial role in the mesenchyme-epithelium interactions during palate development. We found that expression of the Bmp4, Fgf10, Msx1 and Osr2 genes is significantly downregulated in the developing palatal mesenchyme in Pax9 mutant embryos. Remarkably, restoration of Osr2 expression in the early palatal mesenchyme through a Pax9(Osr2KI) allele rescued posterior palate morphogenesis in the absence of Pax9 protein function. Our data indicate that Pax9 regulates a molecular network involving the Bmp4, Fgf10, Shh and Osr2 pathways to control palatal shelf patterning and morphogenesis.
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.forename: Yu
authors.initials: Y
authors.lastname: Lan
authors.forename: Shihai
authors.initials: S
authors.lastname: Jia
authors.forename: Rulang
authors.initials: R
authors.lastname: Jiang
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D049109:Cell Proliferation; D002972:Cleft Palate / Q000235:genetics; D051526:Fibroblast Growth Factor 10 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000378:metabolism; D051957:MSX1 Transcription Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics*; D051764:PAX9 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D010159:Palate / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D053823:Hedgehog Proteins; D051957:MSX1 Transcription Factor; C484084:Msx1 protein, mouse; C438618:Osr2 protein, mouse; D051764:PAX9 Transcription Factor; D051761:Paired Box Transcription Factors; C488759:Pax9 protein, mouse; C465570:Shh protein, mouse; D014157:Transcription Factors
keywords: Bmp4; Cleft palate; Mouse; Osr2; Pax9; Shh