title: Osteo-chondroprogenitor cells are derived from Sox9 expressing precursors.
abstract: The transcription factor Sox9 is expressed in all chondroprogenitors and has an essential role in chondrogenesis. Sox9 is also expressed in other tissues, including central nervous system, neural crest, intestine, pancreas, testis, and endocardial cushions, and plays a crucial role in cell proliferation and differentiation in several of these tissues. To determine the cell fate of Sox9-expressing cells during mouse embryogenesis, we generated mice in which a Cre recombinase gene preceded by an internal ribosome entry site was inserted into the 3' untranslated region of the Sox9 gene (Sox9-Cre knock-in). In the developing skeleton, Sox9 was expressed before Runx2, an early osteoblast marker gene. Cell fate mapping by using Sox9-Cre;ROSA26 reporter (R26R) mice revealed that Sox9-expressing limb bud mesenchymal cells gave rise to both chondrocytes and osteoblasts. Furthermore, a mutant in which the Osterix gene was inactivated in Sox9-expressing cells exhibited a lack of endochondral and intramembranous ossification and a lack of mature osteoblasts comparable with Osterix-null mutants. In addition, Sox9-expressing limb bud mesenchymal cells also contributed to tendon and synovium formation. By using Sox9-Cre;R26R mice, we also were able to systematically follow Sox9-expressing cells from embryonic day 8.0 to 17.0. Our results showed that Sox9-expressing cells contributed to the formation of all cell types of the spinal cord, epithelium of the intestine, pancreas, and mesenchyme of the testis. Thus, our results strongly suggest that all osteo-chondroprogenitor cells, as well as progenitors in a variety of tissues, are derived from Sox9-expressing precursors during mouse embryogenesis.
authors.affiliation: Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. hakiyama@kuhp.kyoto-u.ac.jp
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Akiyama
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Nakashima
authors.forename: Gener
authors.initials: G
authors.lastname: Balmes
authors.forename: Naomi
authors.initials: N
authors.lastname: Iwai
authors.forename: Jian Min
authors.initials: JM
authors.lastname: Deng
authors.forename: Zhaoping
authors.initials: Z
authors.lastname: Zhang
authors.forename: James F
authors.initials: JF
authors.lastname: Martin
authors.forename: Richard R
authors.initials: RR
authors.lastname: Behringer
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Benoit
authors.initials: B
authors.lastname: de Crombrugghe
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D017931:DNA Primers; D047108:Embryonic Development / Q000502:physiology*; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D019426:Integrases / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated; D055758:SOX9 Transcription Factor; D000076182:Sp7 Transcription Factor; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D006609:High Mobility Group Proteins; D011506:Proteins; D022661:RNA, Untranslated; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; C045073:Cre recombinase; D019426:Integrases