State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
Development. 2012 Dec;139(24):4591-600. doi: 10.1242/dev.083055. Epub 2012 Nov 7.
The precise formation of three-dimensional motor circuits is essential for movement control. Within these circuits, motoneurons (MNs) are specified from spinal progenitors by dorsoventral signals and distinct transcriptional programs. Different MN subpopulations have stereotypic cell body positions and show specific spatial axon trajectories. Our knowledge of MN axon outgrowth remains incomplete. Here, we report a zebrafish gene-trap mutant, short lightning (slg), in which prdm14 expression is disrupted. slg mutant embryos show shortened axons in caudal primary (CaP) MNs resulting in defective embryonic movement. Both the CaP neuronal defects and behavior abnormality of the mutants can be phenocopied by injection of a prdm14 morpholino into wild-type embryos. By removing a copy of the inserted transposon from homozygous mutants, prdm14 expression and normal embryonic movement were restored, confirming that loss of prdm14 expression accounts for the observed defects. Mechanistically, Prdm14 protein binds to the promoter region of islet2, a known transcription factor required for CaP development. Notably, disruption of islet2 function caused similar CaP axon outgrowth defects as observed in slg mutant embryos. Furthermore, overexpression of islet2 in slg mutant embryos rescued the shortened CaP axon phenotypes. Together, these data reveal that prdm14 regulates CaP axon outgrowth through activation of islet2 expression.
三维运动电路的精确形成对于运动控制至关重要。在这些电路中，运动神经元（MNs）通过背腹信号和不同的转录程序从脊髓祖细胞中特化而来。不同的 MN 亚群具有刻板的胞体位置，并表现出特定的空间轴突轨迹。我们对 MN 轴突生长的了解仍不完整。在这里，我们报告了一种斑马鱼基因捕获突变体 slg，其中 prdm14 的表达被破坏。slg 突变体胚胎中的尾侧初级（CaP）MNs 的轴突缩短，导致胚胎运动缺陷。突变体的 CaP 神经元缺陷和行为异常都可以通过向野生型胚胎注射 prdm14 形态发生素来模拟。通过从纯合突变体中去除插入转座子的一个拷贝，prdm14 的表达和正常的胚胎运动得到恢复，这证实了缺失 prdm14 表达是导致观察到的缺陷的原因。从机制上讲，Prdm14 蛋白结合到已知对 CaP 发育至关重要的转录因子 islet2 的启动子区域。值得注意的是，islet2 功能的破坏导致了与 slg 突变体胚胎中观察到的类似的 CaP 轴突生长缺陷。此外，在 slg 突变体胚胎中过表达 islet2 挽救了缩短的 CaP 轴突表型。总之，这些数据表明 prdm14 通过激活 islet2 的表达来调节 CaP 轴突的生长。
