A Single-Cell Transcriptomic Map of the Developing Atoh1 Lineage Identifies Neural Fate Decisions and Neuronal Diversity in the Hindbrain

Authors

Jessica C Butts
Sih-Rong Wu
Mark A Durham
Ryan S Dhindsa
Jean-Pierre Revelli
M Cecilia Ljungberg
Olivier Saulnier
Madison E McLaren
Michael D Taylor
Huda Y Zoghbi

Language

English

Publication Date

8-19-2024

Journal

Developmental Cell

DOI

10.1016/j.devcel.2024.07.007

PMID

39106860

PMCID

PMC12374751

PubMedCentral® Posted Date

8-25-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Proneural transcription factors establish molecular cascades to orchestrate neuronal diversity. One such transcription factor, Atonal homolog 1 (Atoh1), gives rise to cerebellar excitatory neurons and over 30 distinct nuclei in the brainstem critical for hearing, breathing, and balance. Although Atoh1 lineage neurons have been qualitatively described, the transcriptional programs that drive their fate decisions and the full extent of their diversity remain unknown. Here, we analyzed single-cell RNA sequencing and ATOH1 DNA binding in Atoh1 lineage neurons of the developing mouse hindbrain. This high-resolution dataset identified markers for specific brainstem nuclei and demonstrated that transcriptionally heterogeneous progenitors require ATOH1 for proper migration. Moreover, we identified a sizable population of proliferating unipolar brush cell progenitors in the mouse Atoh1 lineage, previously described in humans as the origin of one medulloblastoma subtype. Collectively, our data provide insights into the developing mouse hindbrain and markers for functional assessment of understudied neuronal populations.

Keywords

Animals, Rhombencephalon, Basic Helix-Loop-Helix Transcription Factors, Mice, Neurons, Cell Lineage, Single-Cell Analysis, Transcriptome, Cell Differentiation, Gene Expression Regulation, Developmental, Neurogenesis, Cell Movement

Published Open-Access

yes

Recommended Citation

Butts, Jessica C; Wu, Sih-Rong; Durham, Mark A; et al., "A Single-Cell Transcriptomic Map of the Developing Atoh1 Lineage Identifies Neural Fate Decisions and Neuronal Diversity in the Hindbrain" (2024). Duncan NRI Faculty and Staff Publications. 125.
https://digitalcommons.library.tmc.edu/duncar_nri_pub/125