Active repression of muscle fate preserves neural lineage identity during cerebellum development
Shaikh, N. M.; Thulabandu, V.; Inoue, A.; Pare, J.; Norrie, J.; Zhang, Q.; Xu, B.; Cao, X.
Show abstract
Cell fate commitment is commonly thought to entail progressive restriction of developmental potential, enforced by passive, heterochromatin-based silencing of alternative lineage programs. Here we show that maintenance of neural identity during cerebellum development instead requires active repression of a starkly divergent fate by the TEAD-INSM1 transcriptional complex. Loss of TEAD1/2 or INSM1 activates the myogenic master regulator Myod1, resulting in neural cells acquiring transcriptional, structural, and metabolic features of skeletal muscle cells. Deletion of Myod1 fully suppresses neural-to-muscle conversion while partially rescuing neural developmental defects. Our results uncover a latent alternative lineage during neurodevelopment and a surprising role for sequence-specific transcription factors in enforcing lineage boundaries, including those previously thought essentially unbreachable, with implications for understanding aberrant differentiation in disease contexts and cell-type evolution.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Heterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice. 96%
- Discovery and characterization of LNCSOX17 as an essential regulator in human endoderm formation 95%
- Transcriptional regulation of neural stem cell expansion in adult hippocampus 95%
Similar papers in this journal
- Developmental HCN channelopathy results in decreased neural progenitor proliferation and microcephaly in mice 97%
- Postmitotic accumulation of histone variant H3.3 in new cortical neurons establishes neuronal chromatin, transcriptome, and identity 96%
- The Relationship between Birth Timing, Circuit Wiring, and Physiological ResponseProperties of Cerebellar Granule Cells 96%
Similar papers in this journal
Similar papers in this journal
- Cross-species transcriptomic and epigenomic analysis reveals key regulators of injury response and neuronal regeneration in vertebrate retinas. 96%
- Evolutionary convergence of sensory circuits in the pallium of amniotes 96%
- Transcriptomic cytoarchitecture reveals principles of human neocortex organization 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.