| Experiment Id | GSE224031 | Name | Atoh1 drives the heterogeneity of the pontine nuclei neurons and promotes their differentiation |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2024-07-10 |
| description | Pontine nuclei (PN) neurons mediate the communication between the cerebral cortex and the cerebellum to refine skilled motor functions. Prior studies have shown 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-function of Atoh1 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 discovered that Atoh1 regulates cell cycle exit, differentiation, migration, and survival of the PN neurons. Importantly, our data revealed six previously not known PN subtypes that are molecularly and spatially distinct. Interestingly, we found the PN subtypes exhibit differential vulnerability to partial loss of Atoh1 function, providing insights into the prominence of PN phenotypes in patients with ATOH1 missense mutations. Atoh1-lineage neurons labeled by TdTomato in mouse hindbrain or PN were enriched by FACS, followed by scRNA-seq with 10X chromium 3' v3.1 kit and NovaSeq 6000. Single-cell transcriptomic profiles of control and mice carrying Atoh1 hypomorphic mutation were compared. |
