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CRMP2 mediates Sema3F-dependent axon pruning and dendritic spine remodeling

J. Ziak, R. Weissova, K. Jeřábková, M. Janikova, R. Maimon, T. Petrasek, B. Pukajova, M. Kleisnerova, M. Wang, MS. Brill, P. Kasparek, X. Zhou, G. Alvarez-Bolado, R. Sedlacek, T. Misgeld, A. Stuchlik, E. Perlson, M. Balastik

. 2020 ; 21 (3) : e48512. [pub] 20200109

Language English Country Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc21020691

Grant support
NV18-04-00085 Agentura Pro Zdravotnický Výzkum České Republiky (Czech Health Research Council) - International
17-30833A Agentura Pro Zdravotnický Výzkum České Republiky (Czech Health Research Council) - International
16-15915S Grantová Agentura České Republiky (GACR) - International
19-03016S Grantová Agentura České Republiky (GACR) - International
682217 Grantová Agentura, Univerzita Karlova (GA UK) - International
524218 Grantová Agentura, Univerzita Karlova (GA UK) - International
1062216 Grantová Agentura, Univerzita Karlova (GA UK) - International
FP/2007-2013 EC | FP7 | FP7 Ideas: European Research Council (FP7 Ideas) - International
616791 EC | FP7 | FP7 Ideas: European Research Council (FP7 Ideas) - International
SFB 870 German-Israeli Foundation for Scientific Research and Development (GIF) - International
EXC2145 DFG, Munich Cluster for Systems Neurology (SyNergy), DFG - International
RVO 68378050 Akademie Věd České Republiky (Akademie věd ČR) - International
LM2015040 Ministerstvo Školství, Mládeže a Tělovýchovy (MEYS) - International
CZ.1.05/2.1.00/19.0395 Ministerstvo Školství, Mládeže a Tělovýchovy (MEYS) - International
LM2015062 Ministerstvo Školství, Mládeže a Tělovýchovy (MEYS) - International
CZ.1.05/1.1.00/02.0109 Ministerstvo Školství, Mládeže a Tělovýchovy (MEYS) - International
CZ.2.16/3.1.00/21547 Ministerstvo Školství, Mládeže a Tělovýchovy (MEYS) - International
LO1419 Ministerstvo Školství, Mládeže a Tělovýchovy (MEYS) - International
CRC870-A11 DFG, Collaborative Research Center - International
NV17-30833A MZ0 CEP Register

Digital library NLK
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Links

PubMed 31919978
DOI 10.15252/embr.201948512
Knihovny.cz E-resources

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.

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