Ghiyamihoor Farshid, Rad Azam Asemi, 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, Room 129 BMSB, 745 Bannatyne Avenue, Winnipeg, MB, R3E 0J9, Canada.
Cerebellum. 2025 May 2;24(4):92. doi: 10.1007/s12311-025-01848-5.
The nuclear transitory zone (NTZ), while crucial during cerebellar development, has remained elusive due to its transient nature and the technical limitations in observing this dynamic structure in vivo. Traditionally considered an assembly point for immature neurons of the prospective cerebellar nuclei, recent studies highlight the NTZ's rich cellular and molecular heterogeneity in the early-developing region at the rostral end of the cerebellar primordium. While much is known about its molecular diversity, the precise functional role of NTZ in cerebellar development remains unclear. This review synthesizes current knowledge of the NTZ, focusing on its developmental origin, cellular and molecular composition, and potential role in regulating cerebellar development. We explore studies primarily conducted in mice, exploring the NTZ development from the rhombic lip, the ventricular zone, and possibly the mesencephalon. Special attention is given to molecules such as TLX3, Contactin-1 (CNTN1), OLIG2, Reelin (RELN), LMX1A, and TBR2, which are prominently expressed in the NTZ during early cerebellar development. Evidence suggests that the NTZ is more than just a neuronal assembly site; its molecular markers and gene expression profile indicate a role in circuit formation and regulation within the cerebellar primordium. We suggest that the NTZ may contribute to early cerebellar circuit formation, potentially acting as a regulator or organizer of cerebellar development. However, caution is necessary in attributing developmental roles solely based on gene expression patterns. Future studies should focus on the functional consequences of gene expression in the NTZ and its interactions with developing cerebellar circuits.
核过渡区（NTZ）在小脑发育过程中至关重要，但由于其短暂性以及在体内观察这一动态结构的技术限制，一直难以捉摸。传统上认为它是未来小脑核未成熟神经元的聚集点，最近的研究突出了NTZ在小脑原基前端早期发育区域丰富的细胞和分子异质性。虽然对其分子多样性了解很多，但NTZ在小脑发育中的确切功能作用仍不清楚。本综述综合了关于NTZ的现有知识，重点关注其发育起源、细胞和分子组成以及在调节小脑发育中的潜在作用。我们探讨了主要在小鼠中进行的研究，探索了NTZ从菱唇、脑室区以及可能从中脑的发育过程。特别关注了诸如TLX3、Contactin-1（CNTN1）、OLIG2、Reelin（RELN）、LMX1A和TBR2等分子，它们在小脑早期发育过程中在NTZ中显著表达。有证据表明，NTZ不仅仅是一个神经元聚集位点；其分子标记和基因表达谱表明它在小脑原基内的回路形成和调节中发挥作用。我们认为NTZ可能有助于早期小脑回路的形成，潜在地充当小脑发育的调节者或组织者。然而，仅基于基因表达模式来归因发育作用时需要谨慎。未来的研究应关注NTZ中基因表达的功能后果及其与发育中小脑回路的相互作用。
