The midline protein regulates axon guidance by blocking the reiteration of neuroblast rows within the Drosophila ventral nerve cord.
The midline protein regulates axon guidance by blocking the reiteration of neuroblast rows within the Drosophila ventral nerve cord.
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DOI：
10.1371/journal.pgen.1004050
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发表时间：
2013
期刊：
影响因子：
4.5
通讯作者：
Bhat KM
中科院分区：
文献类型：
--
作者：
Manavalan MA;Gaziova I;Bhat KM
引导轴突生长锥体朝向它们的目标是发生在发育中的神经系统的一个基本过程。轴突引导涉及几个主要的信号系统，这些系统的破坏会导致轴突引导缺陷。然而，轴突导航的环境在调节轴突引导中的具体作用还没有被详细研究。在果蝇中，腹神经索被分成几节，半节和前体神经母细胞在单独的半节中成行和成列形成。神经外胚层中节段极性基因的行状表达为神经母细胞提供了最初的行状特征。在这里，我们表明，在编码T-box DNA结合蛋白的中线基因突变的胚胎中，ROW-2神经母细胞和它们的神经外胚层采用了ROW-5的身份。第五排的这种重复最终形成了一个不允许的区域或屏障，这阻止了神经元间纵束沿着其正常的前后路径延伸。虽然我们不知道屏障的性质，但轴索要么在到达这个区域时停滞，要么穿过中线或沿着这个区域向外围投射。此前，我们已经证明，中线确保了神经元谱系中依赖祖先的命运指定。这些结果为中线突变体的轴突导向缺陷提供了分子基础，并说明了适当的环境规范对轴突导向的意义。这些结果还揭示了节段极性在引导轴突从一个节段到下一个节段的重要性，以及建立广泛的节段同一性和轴突指导之间的联系。在神经系统发育期间，一旦由神经母细胞形成，神经元就会朝着它们的突触伙伴的方向生长轴突。遗传力引导这些轴突生长锥体朝向目标。这被称为轴突引导或寻路。有许多蛋白质调节轴突的寻路。众所周知的例子是狭缝及其感受器环形交叉路口，以及Netrin及其感受器磨损。果蝇胚胎和神经系统被分割基因分割成多个片段。片段基因的突变会影响轴突引导，尽管它们是如何做到这一点的还不是很清楚。在我们这里描述的工作中，我们证明了T-box蛋白中线防止了神经母细胞行的错误指定，特别是它防止了第2行变成第5行。因此，在中线突变体中，第2行变成了第5行，最终形成了一种不允许的屏障，阻止轴突遵循他们定义的路径。因此，当轴突到达这一障碍时，它们停止并发散。我们的结果表明，片段基因的突变如何影响轴突引导，以及环境对轴突路径寻找的重要性。我们的工作也是一个警示，我们需要谨慎地解释指导缺陷，并可能因各种其他缺陷而出现。
Guiding axon growth cones towards their targets is a fundamental process that occurs in a developing nervous system. Several major signaling systems are involved in axon-guidance, and disruption of these systems causes axon-guidance defects. However, the specific role of the environment in which axons navigate in regulating axon-guidance has not been examined in detail. In Drosophila, the ventral nerve cord is divided into segments, and half-segments and the precursor neuroblasts are formed in rows and columns in individual half-segments. The row-wise expression of segment-polarity genes within the neuroectoderm provides the initial row-wise identity to neuroblasts. Here, we show that in embryos mutant for the gene midline, which encodes a T-box DNA binding protein, row-2 neuroblasts and their neuroectoderm adopt a row-5 identity. This reiteration of row-5 ultimately creates a non-permissive zone or a barrier, which prevents the extension of interneuronal longitudinal tracts along their normal anterior-posterior path. While we do not know the nature of the barrier, the axon tracts either stall when they reach this region or project across the midline or towards the periphery along this zone. Previously, we had shown that midline ensures ancestry-dependent fate specification in a neuronal lineage. These results provide the molecular basis for the axon guidance defects in midline mutants and the significance of proper specification of the environment to axon-guidance. These results also reveal the importance of segmental polarity in guiding axons from one segment to the next, and a link between establishment of broad segmental identity and axon guidance. During nervous system development, once formed from neuroblasts, neurons grow axons in the direction of their synaptic partners. Genetic forces guide these axon growth cones towards the target. This is known as axon guidance or pathfinding. There are a number of proteins that regulate axon-pathfinding. The well-known examples are the Slit and its receptor Roundabout, and Netrin and its receptor Frazzled. The Drosophila embryo and the nervous system are divided into segments by segmentation genes. Mutations in segmentation genes affect axon guidance, although how they do so is not well understood. In our work described here, we show that the T-box protein Midline prevents mis-specification of neuroblast rows, in particular, it prevents row 2 from becoming row 5. Thus, in midline mutants, row 2 changes into row 5, ultimately creating a non-permissive barrier that prevents axons from following their defined path. Thus, axons stop and diverge when they reach this barrier. Our results show how mutations in segmentation genes can affect axon guidance and how significant the environment is for axon-pathfinding. Our work is also a cautionary reminder that guidance defects need to be interpreted with care and can arise due to a variety of other defects.
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