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Updated: Jun 4, 2026

Genetic Manipulation of Cerebellar Granule Neurons In Vitro and In Vivo to Study Neuronal Morphology and Migration
Published on: March 17, 2014
CRMP5 (collapsin response mediator protein 5) regulates dendritic development and synaptic plasticity in the
Naoya Yamashita1, Bedrich Mosinger, Arpita Roy
1Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Insights
Collapsin response mediator protein 5 (CRMP5) deficiency impairs cerebellar Purkinje cell development and synaptic plasticity. CRMP5 is crucial for brain-derived neurotrophic factor (BDNF) signaling, impacting neuronal structure and function.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- Collapsin response mediator protein 5 (CRMP5) is abundant in the developing brain.
- CRMP family proteins play roles in neuronal development and axon guidance.
Purpose of the Study:
- To investigate the in vivo function of CRMP5 in cerebellar development and synaptic plasticity.
- To elucidate the role of CRMP5 in brain-derived neurotrophic factor (BDNF) signaling.
Main Methods:
- Generation of crmp5-deficient (crmp5(-/-)) mice.
- Immunofluorescence studies of cerebellar Purkinje cells.
- Electrophysiological recordings in cerebellar slices.
- Neuronal culture and stimulation with BDNF.
Main Results:
- crmp5(-/-) mice exhibited aberrant Purkinje cell dendrite morphology and reduced soma size.
- Deficient long-term depression of excitatory synaptic transmission in crmp5(-/-) cerebellar slices.
- BDNF-induced dendritic branching was attenuated in cultured crmp5(-/-) neurons.
- CRMP5 was tyrosine phosphorylated upon coexpression with TrkB, the BDNF receptor.
Conclusions:
- CRMP5 is essential for the proper development, maintenance, and synaptic plasticity of cerebellar Purkinje cells.
- CRMP5 plays a significant role in BDNF signaling pathways, influencing neuronal structure and function.
Abstract:
Collapsin response mediator protein 5 (CRMP5) is one of the CRMP members that expresses abundantly in the developing brain. To examine the in vivo function of CRMP5, we generated crmp5-deficient (crmp5(-/-)) mice. Anti-calbindin immunofluorescence studies of crmp5(-/-) mice revealed aberrant dendrite morphology; specifically, a decrease in the size of soma and diameter of primary dendrite of the cerebellar Purkinje cells at postnatal day 21 (P21) and P28, but not at P14. Coincidentally, CRMP5 is detected in Purkinje cells at P21 and P28 from crmp5(+/-) mice. In cerebellar slices of crmp5(-/-) mice, the induction of long-term depression of excitatory synaptic transmission between parallel fibers and Purkinje cells was deficient. Given that brain-derived neurotrophic factor (BDNF) plays major roles in dendritic development, we tried to elucidate the possible roles of CRMP5 in BDNF signaling. The effect of BDNF to induce dendritic branching was markedly attenuated in cultured crmp5(-/-) neurons. Furthermore, CRMP5 was tyrosine phosphorylated when coexpressed with neurotrophic tyrosine kinase receptor type 2 (TrkB), a receptor for BDNF, in HEK293T cells. These findings suggest that CRMP5 is involved in the development, maintenance and synaptic plasticity of Purkinje cells.
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