TY - JOUR
T1 - The Transcription Factors L-Sox5 and Sox6 Are Essential for Cartilage Formation
AU - Smits, Patrick
AU - Li, Ping
AU - Mandel, Jennifer
AU - Zhang, Zhaoping
AU - Deng, Jian Ming
AU - Behringer, Richard R.
AU - De Crombrugghe, Benoit
AU - Lefebvre, Véronique
N1 - Funding Information:
We thank H. Akiyama, P. Ducy, K. Nakashima, Y. Mishina, M. Sirito, W. Shawlot, and D. Whitworth for helpful technical advice; A. Bradley, K.S.E. Cheah, C.X. Deng, R. Fässler, J. Hecht, M. Höök, H. Kronenberg, F. Luyten, M.P. Scott, T. Shinomura, E. Vuorio, M. Wakamiya, Z. Werb, and Y. Yamada for cells, plasmids, and probes; and G. Karsenty and P. Ducy for critically reading the manuscript. This work was funded by NIH grant AR42919 to B.d.C. and R.R.B, an Arthritis Foundation Investigator Award to V.L., and NIH grant AR46249 to V.L. DNA sequencing was performed by M.D. Anderson Cancer Center sequencing core facility, supported by NCI grant CA16672.
PY - 2001/8
Y1 - 2001/8
N2 - L-Sox5 and Sox6 are highly identical Sry-related transcription factors coexpressed in cartilage. Whereas Sox5 and Sox6 single null mice are born with mild skeletal abnormalities, Sox5; Sox6 double null fetuses die with a severe, generalized chondrodysplasia. In these double mutants, chondroblasts poorly differentiate. They express the genes for all essential cartilage extracellular matrix components at low or undetectable levels and initiate proliferation after a long delay. All cartilages are thus extracellular matrix deficient and remain rudimentary. While chondroblasts in the center of cartilages ultimately activate prehypertrophic chondrocyte markers, epiphyseal chondroblasts ectopically activate hypertrophic chondrocyte markers. Thick intramembranous bone collars develop, but the formation of cartilage growth plates and endochondral bones is disrupted. L-Sox5 and Sox6 are thus redundant, potent enhancers of chondroblast functions, thereby essential for endochondral skeleton formation.
AB - L-Sox5 and Sox6 are highly identical Sry-related transcription factors coexpressed in cartilage. Whereas Sox5 and Sox6 single null mice are born with mild skeletal abnormalities, Sox5; Sox6 double null fetuses die with a severe, generalized chondrodysplasia. In these double mutants, chondroblasts poorly differentiate. They express the genes for all essential cartilage extracellular matrix components at low or undetectable levels and initiate proliferation after a long delay. All cartilages are thus extracellular matrix deficient and remain rudimentary. While chondroblasts in the center of cartilages ultimately activate prehypertrophic chondrocyte markers, epiphyseal chondroblasts ectopically activate hypertrophic chondrocyte markers. Thick intramembranous bone collars develop, but the formation of cartilage growth plates and endochondral bones is disrupted. L-Sox5 and Sox6 are thus redundant, potent enhancers of chondroblast functions, thereby essential for endochondral skeleton formation.
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U2 - 10.1016/S1534-5807(01)00003-X
DO - 10.1016/S1534-5807(01)00003-X
M3 - Article
C2 - 11702786
AN - SCOPUS:0035431807
SN - 1534-5807
VL - 1
SP - 277
EP - 290
JO - Developmental cell
JF - Developmental cell
IS - 2
ER -