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Updated: Jul 15, 2026

Quantitative Analysis of Alternative Pre-mRNA Splicing in Mouse Brain Sections Using RNA In Situ Hybridization Assay
Published on: August 26, 2018
MBNL1-dependent alternative splicing promotes neuronal differentiation through regulation of NUMA1 exon 16 during
Jun Li1, Qiu-Shuang Long2, Ruo-Qi Zhang2
1Brain Research Center and State Key Laboratory of Trauma, Burns, and Combined Injury, The Army Medical University (Third Military Medical University), Chongqing, China.
Introduction:
Direct neuronal reprogramming enables the generation of neurons from somatic cells without passing through a pluripotent state, yet the post-transcriptional mechanisms that refine neuronal identity after fate induction remain poorly understood.
Methods:
We examined alternative splicing during fibroblast-to-neuron reprogramming and investigated the effects of MBNL1 knockdown on neuronal phenotype, transcriptomic and splicing changes, and NUMA1 exon 16 regulation.
Results:
MBNL1 knockdown establishes a distinct reprogramming state (AMmnp) characterized by enhanced neurite outgrowth and a more neuron-like differentiated phenotype, without significantly affecting conversion efficiency. Among MBNL1-dependent transcriptomic and splicing changes, NUMA1 exon 16 emerges as a key target, with exon inclusion reducing neuronal marker expression specifically in the AMmnp context, whereas exon skipping is associated with a more permissive neuronal phenotypic output.
Discussion:
Together, these findings position alternative splicing as an active regulatory layer that shapes neuronal identity and phenotypic output during reprogramming, linking MBNL1-dependent splicing control to cytoskeletal remodeling and neuronal differentiation.
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