title: Odd-skipped related-1 controls neural crest chondrogenesis during tongue development.
abstract: The tongue is a critical element of the feeding system in tetrapod animals for their successful adaptation to terrestrial life. Whereas the oral part of the mammalian tongue contains soft tissues only, the avian tongue has an internal skeleton extending to the anterior tip. The mechanisms underlying the evolutionary divergence in tongue skeleton formation are completely unknown. We show here that the odd-skipped related-1 (Osr1) transcription factor is expressed throughout the neural crest-derived tongue mesenchyme in mouse, but not in chick, embryos during early tongue morphogenesis. Neural crest-specific inactivation of Osr1 resulted in formation of an ectopic cartilage in the mouse tongue, reminiscent in shape and developmental ontogeny of the anterior tongue cartilage in chick. SRY-box containing gene-9 (Sox9), the master regulator of chondrogenesis, is widely expressed in the nascent tongue mesenchyme at the onset of tongue morphogenesis but its expression is dramatically down-regulated concomitant with activation of Osr1 expression in the developing mouse tongue. In Osr1 mutant mouse embryos, expression of Sox9 persisted in the developing tongue mesenchyme where chondrogenesis is subsequently activated to form the ectopic cartilage. Furthermore, we show that Osr1 binds to the Sox9 gene promoter and that overexpression of Osr1 suppressed expression of endogenous Sox9 mRNAs and Sox9 promoter-driven reporter. These data indicate that Osr1 normally prevents chondrogenesis in the mammalian tongue through repression of Sox9 expression and suggest that changes in regulation of Osr1 expression in the neural crest-derived tongue mesenchyme underlie the evolutionary divergence of birds from other vertebrates in tongue morphogenesis.
authors.affiliation: Divisions of Developmental Biology and Plastic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
authors.forename: Han
authors.initials: H
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Lan
authors.forename: Jingyue
authors.initials: J
authors.lastname: Xu
authors.forename: Ching-Fang
authors.initials: CF
authors.lastname: Chang
authors.forename: Samantha A
authors.initials: SA
authors.lastname: Brugmann
authors.forename: Rulang
authors.initials: R
authors.lastname: Jiang
mesh_terms: D000818:Animals; D005075:Biological Evolution; D002642:Chick Embryo; D020219:Chondrogenesis / Q000502:physiology*; D005697:Galactosides; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D017403:In Situ Hybridization; D007211:Indoles; D008156:Luciferases; D051379:Mice; D008822:Mice, Transgenic; D009432:Neural Crest / Q000378:metabolism / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055758:SOX9 Transcription Factor / Q000378:metabolism; D017423:Sequence Analysis, RNA; D013045:Species Specificity; D014059:Tongue / Q000196:embryology* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D005697:Galactosides; D007211:Indoles; C121641:Osr1 protein, mouse; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D014157:Transcription Factors; D008156:Luciferases; D001616:beta-Galactosidase; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside
keywords: cell fate; craniofacial; differentiation; tongue-tie