ABSTRACT
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 nuclear transitory zone (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 Atoh1−/− 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.
SIGNIFICANCE STATEMENT The cerebellum contains a variety of distinct neuronal populations, each playing a significant role in its function within the brain. This research demonstrates that a particular subset of cerebellar nuclei neurons originates from a previously unrecognized germinal zone specific to the cerebellar primordium, independently of Atoh1’s influence.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
We have simplified the technical language throughout the manuscript and included additional background information, particularly in the introduction and discussion sections, to better orient general readers. We have replaced the cartoon with a revised version that provides more detailed information to clarify and simplify the origins of cerebellar nuclei from the caudal and rostral ends in both Atoh1+/+ and Atoh1−/− mice.
