Osteo-chondroprogenitor cells are derived from Sox9 expressing precursors

Haruhiko Akiyama‡; Jung-Eun Kim‡; Kazuhisa Nakashima; Gener Balmes; Naomi Iwai; Jian Min Deng; Zhaoping Zhang; James F. Martin; Richard R. Behringer; Takashi Nakamura; Benoit de Crombrugghe

doi:10.1073/pnas.0504750102

journal article Oct 03, 2005

Osteo-chondroprogenitor cells are derived from Sox9 expressing precursors

Haruhiko Akiyama‡ Jung-Eun Kim‡ Kazuhisa Nakashima Gener Balmes Naomi Iwai Jian Min Deng Zhaoping Zhang James F. Martin

Richard R. Behringer Takashi Nakamura

Benoit de Crombrugghe

Proceedings of the National Academy of Sciences Vol. 102 No. 41 pp. 14665-14670 · Proceedings of the National Academy of Sciences

View at Publisher Save 10.1073/pnas.0504750102

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.

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Metrics

526

Citations

29

References

Details

Published: Oct 03, 2005
Vol/Issue: 102(41)
Pages: 14665-14670

Authors

H

Haruhiko Akiyama‡

Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030; Department of Orthopaedics, Kyoto University, Kyoto 606-8507, Japan; Department of Molecular Pharmacology, Medical Research Institute, and Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 101-0062, Japan; and Alkek Institute of Biosciences and Technology, Texas A & M System Health Science...

J

Jung-Eun Kim‡

Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030; Department of Orthopaedics, Kyoto University, Kyoto 606-8507, Japan; Department of Molecular Pharmacology, Medical Research Institute, and Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 101-0062, Japan; and Alkek Institute of Biosciences and Technology, Texas A & M System Health Science...

K

Kazuhisa Nakashima

Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030; Department of Orthopaedics, Kyoto University, Kyoto 606-8507, Japan; Department of Molecular Pharmacology, Medical Research Institute, and Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 101-0062, Japan; and Alkek Institute of Biosciences and Technology, Texas A & M System Health Science...

G

Gener Balmes

Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030; Department of Orthopaedics, Kyoto University, Kyoto 606-8507, Japan; Department of Molecular Pharmacology, Medical Research Institute, and Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 101-0062, Japan; and Alkek Institute of Biosciences and Technology, Texas A & M System Health Science...

N

Naomi Iwai

Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030; Department of Orthopaedics, Kyoto University, Kyoto 606-8507, Japan; Department of Molecular Pharmacology, Medical Research Institute, and Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 101-0062, Japan; and Alkek Institute of Biosciences and Technology, Texas A & M System Health Science...

J

Jian Min Deng

Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030; Department of Orthopaedics, Kyoto University, Kyoto 606-8507, Japan; Department of Molecular Pharmacology, Medical Research Institute, and Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 101-0062, Japan; and Alkek Institute of Biosciences and Technology, Texas A & M System Health Science...

Z

Zhaoping Zhang

Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030; Department of Orthopaedics, Kyoto University, Kyoto 606-8507, Japan; Department of Molecular Pharmacology, Medical Research Institute, and Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 101-0062, Japan; and Alkek Institute of Biosciences and Technology, Texas A & M System Health Science...

J

James F. Martin

Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030; Department of Orthopaedics, Kyoto University, Kyoto 606-8507, Japan; Department of Molecular Pharmacology, Medical Research Institute, and Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 101-0062, Japan; and Alkek Institute of Biosciences and Technology, Texas A & M System Health Science...

R

Richard R. Behringer

Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030; Department of Orthopaedics, Kyoto University, Kyoto 606-8507, Japan; Department of Molecular Pharmacology, Medical Research Institute, and Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 101-0062, Japan; and Alkek Institute of Biosciences and Technology, Texas A & M System Health Science...

T

Takashi Nakamura

Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030; Department of Orthopaedics, Kyoto University, Kyoto 606-8507, Japan; Department of Molecular Pharmacology, Medical Research Institute, and Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 101-0062, Japan; and Alkek Institute of Biosciences and Technology, Texas A & M System Health Science...

B

Benoit de Crombrugghe

Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030; Department of Orthopaedics, Kyoto University, Kyoto 606-8507, Japan; Department of Molecular Pharmacology, Medical Research Institute, and Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 101-0062, Japan; and Alkek Institute of Biosciences and Technology, Texas A & M System Health Science...

Cite This Article

Haruhiko Akiyama‡, Jung-Eun Kim‡, Kazuhisa Nakashima, et al. (2005). Osteo-chondroprogenitor cells are derived from Sox9 expressing precursors. Proceedings of the National Academy of Sciences, 102(41), 14665-14670. https://doi.org/10.1073/pnas.0504750102

Osteo-chondroprogenitor cells are derived from Sox9 expressing precursors

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