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The ER/Golgi Protein FNDC3B Facilitates Climbing Fibre to Purkinje Cell Synapse Elimination in the Developing Mouse

Céline Louise Mercier1, Takaki Watanabe1,2,3, Yuto Okuno1,3

  • 1Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

The European Journal of Neuroscience
|January 23, 2026
PubMed

Insights

Fibronectin type III domain containing 3B (FNDC3B) protein is essential for eliminating extra climbing fiber (CF) synapses in the developing cerebellum. Loss of FNDC3B impairs synapse elimination, impacting neural circuit refinement.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Cell Biology

Background:

  • Synapse elimination refines neural circuits during development.
  • In the neonatal cerebellum, Purkinje cells (PCs) receive multiple climbing fiber (CF) inputs.
  • Postnatal development involves eliminating supernumerary CFs to establish single innervation of PCs.

Purpose of the Study:

  • To investigate the role of fibronectin type III domain containing 3B (FNDC3B) in CF synapse elimination in the developing mouse cerebellum.
  • To identify molecular mechanisms underlying PC innervation refinement.

Main Methods:

  • Utilized Purkinje cell (PC)-specific RNAi knockdown (KD) screening.
  • Generated PC-selective FNDC3B conditional knockout (FNDC3B-cKO) mice.
  • Analyzed CF synapse elimination, CF extension along PC dendrites, and synaptic inputs at various postnatal days (P9, P10, P21, P40).

Main Results:

  • FNDC3B mRNA is expressed in PCs during CF synapse elimination.
  • PC-selective FNDC3B-cKO mice exhibited impaired CF synapse elimination from P10.
  • Reduced CF extension along PC dendrites was observed in FNDC3B-cKO mice at P21, with recovery by P40.
  • Excitatory and inhibitory synaptic inputs to PCs were unaffected.

Conclusions:

  • FNDC3B facilitates CF synapse elimination in the developing cerebellum.
  • FNDC3B plays a novel role in refining cerebellar neural circuits.
  • The protein is crucial for proper synapse elimination during postnatal development.

Keywords:
FNDC3BPurkinje cellcerebellumclimbing fiberpostnatal developmentsynapse elimination

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