Healy C, Uwanogho D, Sharpe P T
Department of Craniofacial Development, GKT Dental Institute, Kings College London, Guy's Hospital.
Dev Dyn. 1999 May;215(1):69-78. doi: 10.1002/(SICI)1097-0177(199905)215:1<69::AID-DVDY8>3.0.CO;2-N.
The HMG-domain transcription factor Sox9 is a known regulator of the type II collagen gene, a major developmentally regulated protein of cartilage. In order to place Sox9 function in skeletogenesis we have investigated the regulation and misexpression of Sox9 in avian embryos. Application of exogenous BMP2 to chick limbs resulted in upregulation of Sox9, concomitant with induction of ectopic cartilage. Ectopic expression of the BMP antagonist Noggin in the limb resulted in loss of Sox9 expression from the developing digits, indicating that Sox9 expression during chondrogenesis is BMP dependent. Misexpression of Sox9 in vivo resulted in ectopic cartilage formation in limbs and in vitro was able to change the aggregation properties of limb mesenchymal cells, suggesting that Sox9 functions at the level of mesenchymal cell condensation. Misexpression of Sox9 in dermomyotomal cells, which normally give rise to the axial musculature and dermis, can result in the diversion of these cells from their normal fates towards the cartilage differentiation programme. These cells not only express type II collagen, but also Pax1, a marker of ventral fate in the developing somite. This suggests that the cell fate decision to follow the cartilage differentiation pathway is regulated at an early stage by Sox9.
HMG结构域转录因子Sox9是II型胶原基因的已知调节因子，II型胶原是软骨中一种主要受发育调控的蛋白质。为了确定Sox9在骨骼发生中的功能，我们研究了Sox9在禽类胚胎中的调节和异常表达情况。将外源性骨形态发生蛋白2（BMP2）应用于鸡胚肢体，导致Sox9上调，同时诱导异位软骨形成。在肢体中异位表达BMP拮抗剂Noggin，导致发育中的指中Sox9表达缺失，这表明软骨形成过程中Sox9的表达依赖于BMP。在体内异常表达Sox9导致肢体中异位软骨形成，在体外能够改变肢体间充质细胞的聚集特性，这表明Sox9在间充质细胞凝聚水平发挥作用。在通常产生轴上肌肉组织和真皮的生皮节肌细胞中异常表达Sox9，可导致这些细胞从其正常命运转向软骨分化程序。这些细胞不仅表达II型胶原，还表达Pax1，Pax1是发育中的体节腹侧命运的标志物。这表明遵循软骨分化途径的细胞命运决定在早期由Sox9调节。
