Rahimi-Balaei Maryam, Amiri Shayan, Lamonerie Thomas, Wu Sih-Rong, Zoghbi Huda Y, Consalez G Giacomo, Goldowitz Daniel, Marzban Hassan
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, Canada.
Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada.
Elife. 2024 Dec 16;13:RP93778. doi: 10.7554/eLife.93778.
Cerebellar nuclei (CN) neurons serve as the primary output of the cerebellum and originate from the cerebellar primordium at early stages of cerebellar development. These neurons are diverse, integrating information from the cerebellar cortex and relaying it to various brain regions. Employing various methodologies, we have characterized a specific subset of CN neurons that do not originate from the rhombic lip or ventricular zone of the cerebellar primordium. Embryos were collected at early stages of development and processed for immunohistochemistry (IHC), western blotting, in situ hybridization (ISH), embryonic culture, DiI labeling, and flow cytometry analysis (FCM). Our findings indicate that a subset of CN neurons expressing α-synuclein (SNCA), OTX2, MEIS2, and p75NTR (NGFR) are located in the rostroventral region of the NTZ. While CN neurons derived from the rhombic lip are positioned in the caudodorsal area of the NTZ in the cerebellar primordium. Utilizing Otx2-GFP and mice, we have determined that these cells do not originate from the germinal zone of the cerebellar primordium. These results suggest the existence of a novel extrinsic germinal zone for the cerebellar primordium, possibly the mesencephalon, from which early CN neurons originate.
小脑核（CN）神经元是小脑的主要输出神经元，在小脑发育早期起源于小脑原基。这些神经元具有多样性，整合来自小脑皮质的信息并将其传递到各个脑区。我们采用了各种方法，鉴定出了CN神经元的一个特定亚群，它们并非起源于小脑原基的菱唇或脑室区。在发育早期收集胚胎，并进行免疫组织化学（IHC）、蛋白质印迹、原位杂交（ISH）、胚胎培养、DiI标记和流式细胞术分析（FCM）。我们的研究结果表明，表达α-突触核蛋白（SNCA）、OTX2、MEIS2和p75神经营养因子受体（p75NTR，NGFR）的CN神经元亚群位于NTZ的吻腹侧区域。而源自菱唇的CN神经元位于小脑原基中NTZ的尾背侧区域。利用Otx2-GFP小鼠，我们确定这些细胞并非起源于小脑原基的生发区。这些结果提示小脑原基存在一个新的外部生发区，可能是中脑，早期CN神经元由此起源。
