CRMP2 mediates Sema3F-dependent axon pruning and dendritic spine remodeling
2019
Regulation of axon guidance and pruning of inappropriate synapses by class 3 semaphorins is key to
development of neural circuits. Collapsin response mediator protein 2 (CRMP2) has been shown to
regulate axon guidance by mediating Semaphorin 3A (Sema3A) signaling and its dysfunction has
been linked to schizophrenia, however, nothing is known about its role in the synapse pruning. Here,
using newly generated crmp2-/- mice we demonstrate that while CRMP2 has only a moderate effect
on Sema3A-dependent axon guidance in vivo, it is essential for Sema3F-dependent axon pruning and
dendritic spine remodeling. We first demonstrate that CRMP2 deficiency interferes with Sema3A
signaling in compartmentalized neuron cultures and leads to a mild defect in axon guidance in
peripheral nerves and corpus callosum. Strikingly, we show that crmp2-/- mice display more
prominent defects in dendritic spine pruning and stereotyped axon pruning in hippocampus and
visual cortex consistent with impaired Sema3F signaling and with autism spectrum disorder (ASD)-
rather than schizophrenia-like phenotype. Indeed, we demonstrate that CRMP2 mediates Sema3Finduced
axon retraction in primary neurons and that crmp2-/- mice display early postnatal behavioral
changes linked to ASD. In conclusion, we demonstrate that CRMP2 is an essential mediator of
Sema3F-dependent synapse pruning and its dysfunction in early postnatal stages shares histological
and behavioral features of ASD.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
84
References
0
Citations
NaN
KQI