ArticleNeuron2021
A hidden threshold in motor neuron gene networks revealed by modulation of miR-218 dose.
Article in Neuron, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Circuit organization and transcriptomic heterogeneity of sympathetic circuits innervating cranial structures.Cell reports · 2026Article
- Targeted blocking of gene splicing can dysregulate intron-embedded primary microRNAs.Communications biology · 2026Article
- NACC2, a molecular effector of miR-132 regulation at the interface between adult neurogenesis and Alzheimer's disease.Scientific reports · 2024Article
- Motor innervation directs the correct development of the mouse sympathetic nervous system.Nature communications · 2024Article
- miR-218 Promotes Dopaminergic Differentiation and Controls Neuron Excitability and Neurotransmitter Release through the Regulation of a Synaptic-Related Genes Network.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Transcriptional control of motor pool formation and motor circuit connectivity by the LIM-HD protein Isl2.eLife · 2023Article
- Article
- MiR34 contributes to spinal muscular atrophy and AAV9-mediated delivery of MiR34a ameliorates the motor deficits in SMA mice.Molecular therapy. Nucleic acids · 2023Article
- Generation of functional posterior spinal motor neurons from hPSCs-derived human spinal cord neural progenitor cells.Cell regeneration (London, England) · 2023Article
- An exploratory approach to identify microRNAs as circulatory biomarker candidates for epilepsy-associated psychiatric comorbidities in an electrical post-status epilepticus model.Scientific reports · 2023Article
- Single-cell transcriptomic analysis reveals diversity within mammalian spinal motor neurons.Nature communications · 2023Article
- microRNA-dependent regulation of gene expression in GABAergic interneurons.Frontiers in cellular neuroscience · 2023Review
- Motor neurons use push-pull signals to direct vascular remodeling critical for their connectivity.Neuron · 2022Article
- Review
- Sequential and additive expression of miR-9 precursors control timing of neurogenesis.Development (Cambridge, England) · 2022Article
- Detecting microRNA-mediated gene regulatory effects in murine neuronal subpopulations.STAR protocols · 2022Article
- Emerging Potential of Exosomal Non-coding RNA in Parkinson's Disease: A Review.Frontiers in aging neuroscience · 2022Review
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Abstract
Disruption of homeostatic microRNA (miRNA) expression levels is known to cause human neuropathology. However, the gene regulatory and phenotypic effects of altering a miRNA's in vivo abundance (rather than its binary gain or loss) are not well understood. By genetic combination, we generated an allelic series of mice expressing varying levels of miR-218, a motor neuron-selective gene regulator associated with motor neuron disease. Titration of miR-218 cellular dose unexpectedly revealed complex, non-ratiometric target mRNA dose responses and distinct gene network outputs. A non-linearly responsive regulon exhibited a steep miR-218 dose-dependent threshold in repression that, when crossed, resulted in severe motor neuron synaptic failure and death. This work demonstrates that a miRNA can govern distinct gene network outputs at different expression levels and that miRNA-dependent phenotypes emerge at particular dose ranges because of hidden regulatory inflection points of their underlying gene networks.
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