Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland; Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland.
Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland.
Neuron. 2014 Mar 19;81(6):1297-1311. doi: 10.1016/j.neuron.2014.01.038. Epub 2014 Feb 20.
Combinations of transcription factors (TFs) instruct precise wiring patterns in the developing nervous system; however, how these factors impinge on surface molecules that control guidance decisions is poorly understood. Using mRNA profiling, we identified the complement of membrane molecules regulated by the homeobox TF Even-skipped (Eve), the major determinant of dorsal motor neuron (dMN) identity in Drosophila. Combinatorial loss- and gain-of-function genetic analyses of Eve target genes indicate that the integrated actions of attractive, repulsive, and adhesive molecules direct eve-dependent dMN axon guidance. Furthermore, combined misexpression of Eve target genes is sufficient to partially restore CNS exit and can convert the guidance behavior of interneurons to that of dMNs. Finally, we show that a network of TFs, comprised of eve, zfh1, and grain, induces the expression of the Unc5 and Beaten-path guidance receptors and the Fasciclin 2 and Neuroglian adhesion molecules to guide individual dMN axons.
转录因子 (TFs) 的组合在发育中的神经系统中指导精确的布线模式；然而，这些因素如何影响控制导向决策的表面分子尚不清楚。我们使用 mRNA 分析鉴定了受同源盒 TF Even-skipped (Eve) 调控的膜分子的成分，Eve 是果蝇背侧运动神经元 (dMN) 身份的主要决定因素。Eve 靶基因的组合缺失和功能获得遗传分析表明，吸引、排斥和粘附分子的综合作用指导 Eve 依赖性 dMN 轴突导向。此外，Eve 靶基因的组合过表达足以部分恢复 CNS 退出，并且可以将中间神经元的导向行为转换为 dMN 的导向行为。最后，我们表明，由 eve、zfh1 和 grain 组成的 TF 网络诱导 Unc5 和 Beaten-path 导向受体以及 Fasciclin 2 和 Neuroglian 粘附分子的表达，以指导单个 dMN 轴突。
