CRMP2 mediates Sema3F‐dependent axon pruning and dendritic spine remodeling

0524173 - FGÚ 2021 RIV US eng J - Journal Article
Žiak, Jakub - Weissová, Romana - Jeřábková, Kateřina - Janíková, Martina - Maimon, R. - Petrásek, Tomáš - Pukajová, Barbora - Kleisnerová, Marie - Wang, M. - Brill, M. S. - Kašpárek, Petr - Zhou, X. - Alvarez-Bolado, G. - Sedláček, Radislav - Misgeld, T. - Stuchlík, Aleš - Perlson, E. - Balaštík, Martin
CRMP2 mediates Sema3F‐dependent axon pruning and dendritic spine remodeling.
Embo Reports. Roč. 21, č. 3 (2020), č. článku e48512. ISSN 1469-221X. E-ISSN 1469-3178
R&D Projects: GA MZd(CZ) NV18-04-00085; GA ČR(CZ) GA16-15915S; GA ČR(CZ) GA19-03016S; GA MZd NV17-30833A; GA MŠMT(CZ) LM2015040; GA MŠMT ED2.1.00/19.0395; GA MŠMT(CZ) ED1.1.00/02.0109; GA MŠMT(CZ) LM2015062; GA MŠMT LO1419
Institutional support: RVO:67985823 ; RVO:68378050
Keywords : axon guidance * collapsin response mediator protein 2 * dendritic spines * semaphorins * synapse pruning
OECD category: Neurosciences (including psychophysiology
Impact factor: 8.807, year: 2020
Method of publishing: Open access
https://doi.org/10.15252/embr.201948512

Regulation of axon guidance and pruning of inappropriate synapses by class 3 semaphorins are key to the development of neural circuits. Collapsin response mediator protein 2 (CRMP2) has been shown to regulate axon guidance by mediating semaphorin 3A (Sema3A) signaling, however, nothing is known about its role in synapse pruning. Here, using newly generated crmp2−/− mice we demonstrate that CRMP2 has a moderate effect on Sema3A‐dependent axon guidance in vivo, and its deficiency leads to a mild defect in axon guidance in peripheral nerves and the corpus callosum. Surprisingly, crmp2−/− mice display prominent defects in stereotyped axon pruning in hippocampus and visual cortex and altered dendritic spine remodeling, which is consistent with impaired Sema3F signaling and with models of autism spectrum disorder (ASD). We demonstrate that CRMP2 mediates Sema3F signaling in primary neurons and that crmp2−/− mice display ASD‐related social behavior changes in the early postnatal period as well as in adults. Together, we demonstrate that CRMP2 mediates Sema3F‐dependent synapse pruning and its dysfunction shares histological and behavioral features of ASD.
Permanent Link: http://hdl.handle.net/11104/0308536