Institute of Neuroscience, University of Oregon, Eugene, OR 97403-1254, USA.
Development. 2013 Jul;140(13):2765-75. doi: 10.1242/dev.090639. Epub 2013 May 22.
The evolution of joints, which afford skeletal mobility, was instrumental in vertebrate success. Here, we explore the molecular genetics and cell biology that govern jaw joint development. Genetic manipulation experiments in zebrafish demonstrate that functional loss, or gain, of the homeobox-containing gene barx1 produces gain, or loss, of joints, respectively. Ectopic joints in barx1 mutant animals are present in every pharyngeal segment, and are associated with disrupted attachment of bone, muscles and teeth. We find that ectopic joints develop at the expense of cartilage. Time-lapse experiments suggest that barx1 controls the skeletal precursor cell choice between differentiating into cartilage versus joint cells. We discovered that barx1 functions in this choice, in part, by regulating the transcription factor hand2. We further show that hand2 feeds back to negatively regulate barx1 expression. We consider the possibility that changes in barx1 function in early vertebrates were among the key innovations fostering the evolution of skeletal joints.
关节的进化为骨骼的活动性提供了条件，这对脊椎动物的成功起到了重要作用。在这里，我们探讨了控制颌关节发育的分子遗传学和细胞生物学。斑马鱼中的基因操作实验表明，含有同源盒的基因 barx1 的功能丧失或获得分别导致关节的获得或丧失。barx1 突变动物的异位关节存在于每个咽段，并与骨、肌肉和牙齿的附着中断有关。我们发现异位关节的形成是以软骨为代价的。延时实验表明，barx1 控制着骨骼前体细胞在分化为软骨与关节细胞之间的选择。我们发现 barx1 通过调节转录因子 hand2 来发挥这一选择作用。我们进一步表明，hand2 通过负反馈调节 barx1 的表达。我们考虑了这样一种可能性，即在早期脊椎动物中，barx1 功能的改变是促进骨骼关节进化的关键创新之一。
