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Sox9 is required for cartilage formation.

W Bi¹, J M Deng, Z Zhang

¹Department of Molecular Genetics, The University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.

Nature Genetics

|May 13, 1999

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SOX9 is a transcription factor essential for chondrocyte lineage development and cartilage formation. Sox9 deficiency prevents chondrogenesis, highlighting its critical role in skeletal development.

Area of Science:

Developmental Biology
Molecular Biology
Genetics

Background:

Chondrogenesis is crucial for skeletal development, involving mesenchyme condensation and chondrocyte differentiation.
While chondrocyte terminal products are known, factors specifying the chondrocyte lineage remain largely unknown.
SOX9, a high-mobility-group domain transcription factor, is expressed in chondrocytes and other tissues.

Purpose of the Study:

To identify factors that specify the chondrocyte lineage.
To investigate the role of SOX9 in chondrogenesis and cartilage formation.

Main Methods:

Analysis of SOX9 expression during embryogenesis.
Challenging Sox9-/- embryonic stem cells in teratomas.
Generating mouse chimeras to assess Sox9-/- cell behavior in vivo.

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Main Results:

Sox9-/- cells were excluded from cartilages in mouse chimeras, forming a non-chondrogenic mesenchyme.
Sox9-/- cells failed to express chondrocyte-specific markers (Col2a1, Col9a2, Col11a2, Agc).
No cartilage formed in teratomas derived from Sox9-/- embryonic stem cells.

Conclusions:

SOX9 is identified as a regulator of the chondrocyte lineage.
SOX9 is essential for chondrocyte differentiation and cartilage formation.
This study identifies SOX9 as the first essential transcription factor for chondrogenesis.