Identification of an Early Subset of Cerebellar Nuclei Neurons in Mice

Authors

Maryam Rahimi-Balaei
Shayan Amiri
Thomas Lamonerie
Sih-Rong Wu
Huda Y Zoghbi
G Giacomo Consalez
Daniel Goldowitz
Hassan Marzban

Publication Date

12-16-2024

Journal

eLife

DOI

10.7554/eLife.93778

PMID

39679919

PMCID

PMC11649241

PubMedCentral® Posted Date

12-16-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Animals, Neurons, Mice, Cerebellar Nuclei, Otx Transcription Factors, Basic Helix-Loop-Helix Transcription Factors, Immunohistochemistry, Mice, Knockout, Flow Cytometry

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 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.