Division of Brain Function, National Institute of Genetics, Mishima, Shizuoka, 411-8540, Japan.
Laboratory of Neuroscience, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, 565-0871, Japan.
Sci Rep. 2017 Sep 20;7(1):11992. doi: 10.1038/s41598-017-12269-8.
Netrin-1 (Ntn1) emanating from the ventral midline has been thought to act as a long-range diffusible chemoattractant for commissural axons (CAs). However, CAs still grow towards the midline in the absence of the floor plate (FP), a glial structure occupying the midline. Here, using genetically loss-of-function approaches in mice, we show that Ntn1 derived from the ventricular zone (VZ), but not the FP, is crucial for CA guidance in the mouse hindbrain. During the period of CA growth, Ntn1 is expressed in the ventral two-thirds of the VZ, in addition to the FP. Remarkably, deletion of Ntn1 from the VZ and even from the dorsal VZ highly disrupts CA guidance to the midline, whereas the deletion from the FP has little impact on it. We also show that the severities of CA guidance defects found in the Ntn1 conditional mutants were irrelevant to their FP long-range chemoattractive activities. Our results are incompatible with the prevailing view that Ntn1 is an FP-derived long-range diffusible chemoattractant for CAs, but suggest a novel mechanism that VZ-derived Ntn1 directs CAs to the ventral midline by its local actions.
神经导向因子 1（Ntn1）从腹侧中线释放，被认为是一种长程弥散趋化因子，吸引连合纤维（CA）。然而，在没有占据中线的基板（floor plate，FP）的情况下，CA 仍然向中线生长。在这里，我们使用小鼠中的基因功能丧失方法表明，来源于脑室区（ventricular zone，VZ）的 Ntn1，但不是 FP，对于小鼠后脑 CA 的引导是至关重要的。在 CA 生长期间，除了 FP 外，Ntn1 还在 VZ 的腹侧三分之二处表达。值得注意的是，从 VZ 甚至从背侧 VZ 中删除 Ntn1 会严重破坏 CA 向中线的引导，而从 FP 中删除对其影响很小。我们还表明，在 Ntn1 条件性突变体中发现的 CA 引导缺陷的严重程度与它们的 FP 长程趋化活性无关。我们的结果与流行的观点不一致，即 Ntn1 是一种 FP 衍生的长程弥散趋化因子，吸引 CA，但表明了一种新的机制，即 VZ 衍生的 Ntn1 通过其局部作用指导 CA 到腹侧中线。
