Tbx16 regulates hox gene activation in mesodermal progenitor cells.
Tbx16 regulates hox gene activation in mesodermal progenitor cells.
复制标题
DOI：
10.1038/nchembio.2124
复制
发表时间：
2016-09
影响因子：
14.8
通讯作者：
Chen JK
中科院分区：
文献类型：
--
作者：
Payumo AY;McQuade LE;Walker WJ;Yamazoe S;Chen JK
转录因子T-box 16（Tbx 16/Spadetail）是斑马鱼（Danio rerio）近轴中胚层发育的重要调控因子。中胚层祖细胞（MPC）不能分化成tbx 16突变体的躯干体节，而是在未成熟状态下积累在尾芽内。Tbx 16控制中胚层模式的机制仍然是个谜，我们在这里描述了可光活化的吗啡寡核苷酸在MPC中确定Tbx 16转录组的应用。我们确定了124 Tbx 16调控的基因在斑马鱼原肠胚中表达，包括几个发育信号蛋白和原肠胚形成，肌发生和体节发生的调节剂。出乎意料的是，我们观察到Tbx 16功能的丧失过早激活MPC中的后部hox基因，并且单个后部hox基因的过表达足以破坏MPC迁移。我们的研究支持一个模型，其中Tbx 16调节共线hox基因激活的时间，以协调前后的命运和近轴MPC的位置。
The transcription factor T-box 16 (Tbx16/Spadetail) is an essential regulator of paraxial mesoderm development in zebrafish (Danio rerio). Mesodermal progenitor cells (MPCs) fail to differentiate into trunk somites in tbx16 mutants and instead accumulate within the tailbud in an immature state. The mechanisms by which Tbx16 controls mesoderm patterning have remained enigmatic, and we describe here the application of photoactivatable morpholino oligonucleotides to determine the Tbx16 transcriptome in MPCs. We identify 124 Tbx16-regulated genes that are expressed in zebrafish gastrulae, including several developmental signaling proteins and regulators of gastrulation, myogenesis, and somitogenesis. Unexpectedly, we observe that loss of Tbx16 function precociously activates posterior hox genes in MPCs, and overexpression of a single posterior hox gene is sufficient to disrupt MPC migration. Our studies support a model in which Tbx16 regulates the timing of collinear hox gene activation to coordinate the anterior-posterior fates and positions of paraxial MPCs.