Liu Ya-Hsin, Jakobsen Janus S, Valentin Guillaume, Amarantos Ioannis, Gilmour Darren T, Furlong Eileen E M
European Molecular Biology Laboratory, Heidelberg, Germany.
Dev Cell. 2009 Feb;16(2):280-91. doi: 10.1016/j.devcel.2009.01.006.
Nk-2 proteins are essential developmental regulators from flies to humans. In Drosophila, the family member tinman is the major regulator of cell fate within the dorsal mesoderm, including heart, visceral, and dorsal somatic muscle. To decipher Tinman's direct regulatory role, we performed a time course of ChIP-on-chip experiments, revealing a more prominent role in somatic muscle specification than previously anticipated. Through the combination of transgenic enhancer-reporter assays, colocalization studies, and phenotypic analyses, we uncovered two additional factors within this myogenic network: by activating eyes absent, Tinman's regulatory network extends beyond developmental stages and tissues where it is expressed; by regulating stat92E expression, Tinman modulates the transcriptional readout of JAK/STAT signaling. We show that this pathway is essential for somatic muscle development in Drosophila and for myotome morphogenesis in zebrafish. Taken together, these data uncover a conserved requirement for JAK/STAT signaling and an important component of the transcriptional network driving myogenesis.
Nk-2蛋白是从果蝇到人类至关重要的发育调节因子。在果蝇中，家族成员tinman是背侧中胚层（包括心脏、内脏和背侧体壁肌肉）内细胞命运的主要调节因子。为了解析Tinman的直接调节作用，我们进行了一系列芯片上的染色质免疫沉淀（ChIP-on-chip）实验，结果显示其在体壁肌肉特化中的作用比之前预期的更为显著。通过转基因增强子-报告基因检测、共定位研究和表型分析相结合，我们在这个肌发生网络中发现了另外两个因子：通过激活无眼基因（eyes absent），Tinman的调节网络扩展到其表达的发育阶段和组织之外；通过调节stat92E的表达，Tinman调节JAK/STAT信号通路的转录输出。我们表明，该信号通路对于果蝇的体壁肌肉发育和斑马鱼的肌节形态发生至关重要。综上所述，这些数据揭示了JAK/STAT信号通路的保守需求以及驱动肌发生的转录网络的一个重要组成部分。
