University of Duisburg-Essen, Center of Medical Biotechnology, Essen, Germany.
Dev Dyn. 2010 Jun;239(6):1818-26. doi: 10.1002/dvdy.22301.
Signaling of Indian hedgehog (Ihh), one of the key regulators of endochondral ossification is mediated by transcription factors of the Gli family, Gli1, Gli2, and Gli3. Gli3 and to a lesser extent Gli2 can be proteolytically processed into short repressor proteins. Upon Ihh signaling, processing is inhibited and the full-length proteins function as activators of transcription. Gli3 has been shown to mainly act as a repressor of Ihh target genes in chondrocytes, but the role of other Gli isoforms is less clear. Analyzing mouse mutants deficient for Ihh;Gli2 or Gli3;Gli2, we show here that the Gli2 repressor has no detectable function in chondrocyte or osteoblast differentiation. Instead, Gli2 seems to act as an activator to fully induce the expression of Ihh target genes in skeletal tissues. Furthermore, we show that, in the absence of Gli3, the activator function of Gli2 is sufficient to induce Ihh-dependent osteoblast differentiation.
信号转导的印度刺猬（Ihh)，是一个关键的调节因子的软骨内骨化是由转录因子的 Gli 家族，Gli1，Gli2，和 Gli3。Gli3 和在较小程度上 Gli2 可以被蛋白水解处理成短的抑制蛋白。在 Ihh 信号转导，处理被抑制和全长蛋白作为转录激活物。Gli3 已被证明主要作为一个抑制物的 Ihh 靶基因在软骨细胞，但其他 Gli 同工型的作用不太清楚。分析小鼠突变体缺乏 Ihh;Gli2 或 Gli3;Gli2，我们在这里表明，该 Gli2 抑制剂没有检测到的功能在软骨细胞或成骨细胞分化。相反，Gli2 似乎作为一个激活剂，以充分诱导表达 Ihh 靶基因在骨骼组织。此外，我们表明，在缺乏 Gli3 的情况下，Gli2 的激活功能足以诱导 Ihh 依赖的成骨细胞分化。
