Bhat Krishna Moorthi
Department of Neuroscience and Cell Biology, University of Texas Medical School, Galveston, TX 77555, USA.
Dev Biol. 2007 Nov 15;311(2):613-22. doi: 10.1016/j.ydbio.2007.09.004. Epub 2007 Sep 17.
Neurons and their precursor cells are formed in different regions within the developing CNS, but they migrate and occupy very specific sites in the mature CNS. The ultimate position of neurons is crucial for establishing proper synaptic connectivity in the brain. In Drosophila, despite its extensive use as a model system to study neurogenesis, we know almost nothing about neuronal migration or its regulation. In this paper, I show that one of the most studied neuronal pairs in the Drosophila nerve cord, RP2/sib, has a complicated migratory route. Based on my studies on Wingless (Wg) signaling, I report that the neuronal migratory pattern is determined at the precursor cell stage level. The results show that Wg activity in the precursor neuroectodermal and neuroblast levels specify neuronal migratory pattern two divisions later, thus, well ahead of the actual migratory event. Moreover, at least two downstream genes, Cut and Zfh1, are involved in this process but their role is at the downstream neuronal level. The functional importance of normal neuronal migration and the requirement of Wg signaling for the process are indicated by the finding that mislocated RP2 neurons in embryos mutant for Wg-signaling fail to properly send out their axon projection.
神经元及其前体细胞在发育中的中枢神经系统(CNS)的不同区域形成,但它们会迁移并在成熟的中枢神经系统中占据非常特定的位置。神经元的最终位置对于在大脑中建立适当的突触连接至关重要。在果蝇中,尽管它被广泛用作研究神经发生的模型系统,但我们对神经元迁移及其调控几乎一无所知。在本文中,我表明果蝇神经索中研究最多的神经元对之一,即RP2/sib,具有复杂的迁移途径。基于我对无翅(Wg)信号通路的研究,我报告神经元迁移模式是在前体细胞阶段确定的。结果表明,前体神经外胚层和神经母细胞水平的Wg活性在两个分裂期后确定神经元迁移模式,因此,远早于实际的迁移事件。此外,至少两个下游基因Cut和Zfh1参与了这一过程,但它们的作用是在下游神经元水平。Wg信号通路突变胚胎中位置错误的RP2神经元无法正确发出轴突投射这一发现表明了正常神经元迁移的功能重要性以及该过程对Wg信号通路的需求。