Atoh1 Drives the Heterogeneity of the Pontine Nuclei Neurons and Promotes Their Differentiation

Authors

Sih-Rong Wu
Jessica C Butts
Matthew S Caudill
Jean-Pierre Revelli
Ryan S Dhindsa
Mark A Durham
Huda Y Zoghbi

Publication Date

6-30-2023

Journal

Science Advances

DOI

10.1126/sciadv.adg1671

PMID

37390208

PMCID

PMC10313176

PubMedCentral® Posted Date

6-30-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Animals, Mice, Cell Differentiation, Cerebellum, Cell Cycle, Cell Division, Neurons, Basic Helix-Loop-Helix Transcription Factors

Abstract

Pontine nuclei (PN) neurons mediate the communication between the cerebral cortex andthe cerebellum to refine skilled motor functions. Prior studies showed that PN neurons fall into two subtypes based on their anatomic location and region-specific connectivity, but the extent of their heterogeneity and its molecular drivers remain unknown. Atoh1 encodes a transcription factor that is expressed in the PN precursors. We previously showed that partial loss of Atoh1 function in mice results in delayed PN development and impaired motor learning. In this study, we performed single-cell RNA sequencing to elucidate the cell state–specific functions of Atoh1 during PN development and found that Atoh1 regulates cell cycle exit, differentiation, migration, and survival of PN neurons. Our data revealed six previously not known PN subtypes that are molecularly and spatially distinct. We found that the PN subtypes exhibit differential vulnerability to partial loss of Atoh1 function, providing insigh