Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
Development. 2012 Aug;139(16):2988-98. doi: 10.1242/dev.078675. Epub 2012 Jul 4.
Sox9 acts together with Sox5 or Sox6 as a master regulator for chondrogenesis; however, the inter-relationship among these transcription factors remains unclear. Here, we show that the protein kinase MLTK plays an essential role in the onset of chondrogenesis through triggering the induction of Sox6 expression by Sox9. We find that knockdown of MLTK in Xenopus embryos results in drastic loss of craniofacial cartilages without defects in neural crest development. We also find that Sox6 is specifically induced during the onset of chondrogenesis, and that the Sox6 induction is inhibited by MLTK knockdown. Remarkably, Sox6 knockdown phenocopies MLTK knockdown. Moreover, we find that ectopic expression of MLTK induces Sox6 expression in a Sox9-dependent manner. Our data suggest that p38 and JNK pathways function downstream of MLTK during chondrogenesis. These results identify MLTK as a novel key regulator of chondrogenesis, and reveal its action mechanism in chondrocyte differentiation during embryonic development.
Sox9 与 Sox5 或 Sox6 一起作为软骨形成的主调控因子发挥作用；然而，这些转录因子之间的相互关系尚不清楚。在这里，我们表明蛋白激酶 MLTK 通过触发 Sox9 诱导 Sox6 表达，在软骨形成的开始中发挥重要作用。我们发现，在非洲爪蟾胚胎中敲低 MLTK 会导致颅面软骨严重缺失，而神经嵴发育没有缺陷。我们还发现 Sox6 在软骨形成开始时特异性诱导，并且 Sox6 诱导被 MLTK 敲低抑制。值得注意的是，Sox6 敲低表型模拟了 MLTK 敲低。此外，我们发现异位表达 MLTK 以 Sox9 依赖的方式诱导 Sox6 表达。我们的数据表明 p38 和 JNK 途径在软骨形成过程中作为 MLTK 的下游发挥作用。这些结果确定了 MLTK 是软骨形成的一个新的关键调节因子，并揭示了它在胚胎发育过程中软骨细胞分化中的作用机制。
