The Nuclear Transitory Zone: A Key Player in the Cerebellar Development.

Abstract

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.