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Related Experiment Video

Updated: Dec 19, 2025

Utilizing In Vivo Postnatal Electroporation to Study Cerebellar Granule Neuron Morphology and Synapse Development
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A Dynamic Splicing Program Ensures Proper Synaptic Connections in the Developing Cerebellum.

Donatella Farini1, Eleonora Cesari2, Robert J Weatheritt3

  • 1Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy; Fondazione Santa Lucia, IRCCS, Rome, Italy.

Cell Reports
|June 4, 2020
PubMed
Summary
This summary is machine-generated.

A dynamic splicing program regulated by Sam68 shapes cerebellar neuronal circuits. This process is vital for motor and cognitive functions, and its disruption leads to neurodevelopmental issues and motor deficits.

Keywords:
Sam68alternative splicingautismcerebellum developmentneuronal activitypersonalized medicinesocial behaviorsynaptogenesis

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Gene expression coordination is critical for developing cerebellar neuronal circuits.
  • Transcriptional changes alone do not fully explain neuronal differentiation.
  • A dynamic splicing program impacting synaptic genes in cerebellar neurons was uncovered.

Purpose of the Study:

  • To investigate the role of splicing in cerebellar development.
  • To identify regulators of splicing in cerebellar neurons.
  • To understand the functional consequences of disrupted splicing in the cerebellum.

Main Methods:

  • Analysis of splicing patterns in cerebellar neurons.
  • Identification of enriched motifs and implicated splicing factors.
  • Experimental ablation of the splicing factor Sam68.
  • Assessment of synaptic function and behavioral outcomes in Sam68-ablated mice.

Main Results:

  • A widespread and dynamic splicing program affecting synaptic genes was identified.
  • The splicing factor Sam68 was implicated as a key regulator, controlling splicing via U2AF competition.
  • Sam68 ablation disrupted splicing of neurodevelopmental disease-associated genes.
  • Purkinje cell synaptic connections and firing were impaired, leading to motor deficits and abnormal social behavior.

Conclusions:

  • A dynamic splicing regulatory network shapes cerebellar synapses during early development.
  • Sam68-mediated alternative splicing is essential for establishing motor and cognitive circuitry.
  • Disruption of this splicing network underlies neurodevelopmental and motor coordination defects.