Department of Human Anatomy and Cell Science, The Children's Hospital Research Institute of Manitoba (CHRIM), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Rm 129 BMSB, 745 Bannatyne Avenue, Winnipeg, MB, R3E 0J9, Canada.
Brain Struct Funct. 2019 Sep;224(7):2421-2436. doi: 10.1007/s00429-019-01916-7. Epub 2019 Jun 29.
In the standard model for the development of climbing and mossy fiber afferent pathways to the cerebellum, the ingrowing axons target the embryonic Purkinje cell somata (around embryonic ages (E13-E16 in mice). In this report, we describe a novel earlier stage in afferent development. Immunostaining for a neurofilament-associated antigen (NAA) reveals the early axon distributions with remarkable clarity. Using a combination of DiI axon tract tracing, analysis of neurogenin1 null mice, which do not develop trigeminal ganglia, and mouse embryos maintained in vitro, we show that the first axons to innervate the cerebellar primordium as early as E9 arise from the trigeminal ganglion. Therefore, early trigeminal axons are in situ before the Purkinje cells are born. Double immunostaining for NAA and markers of the different domains in the cerebellar primordium reveal that afferents first target the nuclear transitory zone (E9-E10), and only later (E10-E11) are the axons, either collaterals from the trigeminal ganglion or a new afferent source (e.g., vestibular ganglia), seen in the Purkinje cell plate. The finding that the earliest axons to the cerebellum derive from the trigeminal ganglion and enter the cerebellar primordium before the Purkinje cells are born, where they seem to target the cerebellar nuclei, reveals a novel stage in the development of the cerebellar afferents.
在小脑 climbing 和 mossy 纤维传入途径发育的标准模型中，生长的轴突以胚胎浦肯野细胞体细胞（胚胎期（E13-E16 在小鼠中）为靶标。在本报告中，我们描述了传入发育的一个新的早期阶段。用神经丝相关抗原（NAA）的免疫染色可清晰地显示早期轴突的分布。我们使用 DiI 轴突束追踪、分析不发育三叉神经节的神经生成素 1 缺失小鼠以及体外培养的小鼠胚胎的组合，表明最早在 E9 时就有轴突开始支配小脑原基，这些轴突来自三叉神经节。因此，早期的三叉神经轴突在浦肯野细胞出生之前就已经存在于原位。NAA 与小脑原基不同区域标志物的双重免疫染色显示，传入纤维首先靶向核过渡区（E9-E10），只有在稍后（E10-E11），来自三叉神经节的轴突或新的传入源（例如前庭神经节）的轴突才能在浦肯野细胞板中被看到。最早到达小脑的轴突来自三叉神经节，并在浦肯野细胞出生之前进入小脑原基，在那里它们似乎靶向小脑核，这揭示了小脑传入纤维发育的一个新阶段。
