title: Msx2 is a repressor of chondrogenic differentiation in migratory cranial neural crest cells.
abstract: During early mouse embryogenesis, cranial neural crest cells (CNCC) emigrate from the posterior midbrain and rhombomeres 1 and 2 of the anterior hindbrain into the first branchial arch-derived maxillary and mandibular processes and there provide cell lineages for several phenotypes, including cartilage, bone, and tooth. Here, we report that Sox9 and Msx2 were coexpressed in a subpopulation of CNCC during their migration. Because Sox9 is a transactivator of chondrogenesis, and Msx genes can act as transcriptional repressors, we hypothesized that Sox9 expression indicates the determination of CNCC-derived chondrogenic cell lineage and that Msx2 represses chondrogenic differentiation until CNCC migration is completed within the mandibular processes. To test whether Msx2 represses chondrogenesis, we designed experiments to inhibit Msx2 function in migratory CNCC in primary cultures through the expression of loss-of-function Msx2 mutants. We showed that infection of migratory CNCC with adenovirus Msx2 mutants accelerated the rate and extent of chondrogenesis, as indicated by the expression level of type II collagen and aggrecan, and the amount of alcian blue staining. Adenovirus infections did not apparently interfere with CNCC proliferation or migration. These findings suggest that an important early event in craniofacial morphogenesis is a transient expression of both Sox9 and Msx2 during emigration into the forming mandibular processes followed by restricted expression of Sox9 within CNCC- derived chondroprogenitor cells. We conclude that Msx2 serves as a repressor of chondrogenic differentiation during CNCC migration.
authors.affiliation: Craniofacial Development Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 6 Center Drive, Bethesda, MD 20892-2745, USA.
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: G H
authors.initials: GH
authors.lastname: Nuckolls
authors.forename: I
authors.initials: I
authors.lastname: Takahashi
authors.forename: K
authors.initials: K
authors.lastname: Nonaka
authors.forename: M
authors.initials: M
authors.lastname: Nagata
authors.forename: T
authors.initials: T
authors.lastname: Ikura
authors.forename: H C
authors.initials: HC
authors.lastname: Slavkin
authors.forename: L
authors.initials: L
authors.lastname: Shum
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D053674:Aggrecans; D000423:Alcian Blue; D000818:Animals; D002356:Cartilage / Q000166:cytology / Q000196:embryology; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology*; D024043:Collagen Type II / Q000235:genetics; D004396:Coloring Agents; D004268:DNA-Binding Proteins / Q000235:genetics*; D016326:Extracellular Matrix Proteins; D018014:Gene Transfer Techniques; D006609:High Mobility Group Proteins / Q000235:genetics; D018398:Homeodomain Proteins; D006801:Humans; D007668:Kidney / Q000166:cytology; D037181:Lectins, C-Type; D008342:Mandibulofacial Dysostosis / Q000235:genetics; D051379:Mice; D016296:Mutagenesis / Q000502:physiology; D009432:Neural Crest / Q000166:cytology* / Q000196:embryology*; D011509:Proteoglycans / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055758:SOX9 Transcription Factor; D013194:Staining and Labeling; D014157:Transcription Factors / Q000235:genetics
chemical_list: C508320:Acan protein, mouse; D053674:Aggrecans; D024043:Collagen Type II; D004396:Coloring Agents; D004268:DNA-Binding Proteins; D016326:Extracellular Matrix Proteins; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D037181:Lectins, C-Type; C084119:MSX2 protein; D011509:Proteoglycans; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C527933:Sox9 protein, mouse; D014157:Transcription Factors; D000423:Alcian Blue