title: Loss of Sox9 function results in defective chondrocyte differentiation of mouse embryonic stem cells in vitro.
abstract: The transcription factor Sox9 plays an important role during chondrogenesis. After early conditional inactivation of Sox9 in mesenchymal limb bud cells of mice, mesenchymal condensations as well as cartilage and bone are completely absent in the developing limbs. We analyzed chondrogenic differentiation of Sox9-/- mouse embryonic stem cells in vitro, using two clones with different targeted mutations. We found that the development of mature and hypertrophic chondrocytes is completely inhibited in the absence of Sox9 confirming that Sox9 is required for the formation of cartilage. In contrast, Sox9+/- mouse embryonic stem cells showed continuous but reduced differentiation into mature chondrocytes. Interestingly, the formation of early chondrogenic condensations expressing characteristic marker genes such as scleraxis, Sox5 and Sox6 was not inhibited in the absence of Sox9 in vitro. Thus, we propose that the earliest step of chondrogenesis could be regulated by a non cell-autonomous function of Sox9.
authors.affiliation: Dept. of Medical Molecular Biology, University of Lubeck, Lubeck, Germany.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Hargus
authors.forename: Ralf
authors.initials: R
authors.lastname: Kist
authors.forename: Jan
authors.initials: J
authors.lastname: Kramer
authors.forename: Daniela
authors.initials: D
authors.lastname: Gerstel
authors.forename: Angela
authors.initials: A
authors.lastname: Neitz
authors.forename: Gerd
authors.initials: G
authors.lastname: Scherer
authors.forename: Jürgen
authors.initials: J
authors.lastname: Rohwedel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002356:Cartilage / Q000166:cytology / Q000254:growth & development; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D019902:Chondrocytes / Q000737:chemistry* / Q000378:metabolism*; D020219:Chondrogenesis / Q000235:genetics / Q000502:physiology; D002999:Clone Cells; D024043:Collagen Type II / Q000235:genetics; D004247:DNA / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D005091:Exons; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D006609:High Mobility Group Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055758:SOX9 Transcription Factor; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
chemical_list: C447413:Col2a1 protein, mouse; D024043:Collagen Type II; D006609:High Mobility Group Proteins; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D014157:Transcription Factors; D004247:DNA