The Transcription Factors L-Sox5 and Sox6 Are Essential for Cartilage Formation

• Published in: Developmental cell Vol. 1; no. 2; pp. 277 - 290
• Main Authors: Smits, Patrick, Li, Ping, Mandel, Jennifer, Zhang, Zhaoping, Deng, Jian Ming, Behringer, Richard R, de Crombrugghe, Benoit, Lefebvre, Véronique
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-08-2001
• Subjects: Animals; Bone and Bones - abnormalities; Bone Development; Cartilage - embryology; Cartilage - physiology; Cell Differentiation; Chondrocytes - cytology; Chondrocytes - metabolism; DNA-Binding Proteins - metabolism; DNA-Binding Proteins - physiology; Exostoses, Multiple Hereditary - genetics; High Mobility Group Proteins - metabolism; High Mobility Group Proteins - physiology; In Situ Hybridization; L-Sox5 protein; Mice; Microscopy, Fluorescence; Models, Biological; Models, Genetic; Mutation; Nuclear Proteins - metabolism; Nuclear Proteins - physiology; Phenotype; Sox6 protein; SOXD Transcription Factors; Transcription Factors
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/S1534-5807(01)00003-X

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.