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CRMP 2 mediates Sema3F‐dependent axon pruning and dendritic spine remodeling
Author(s) -
Ziak Jakub,
Weissova Romana,
Jeřábková Kateřina,
Janikova Martina,
Maimon Roy,
Petrasek Tomas,
Pukajova Barbora,
Kleisnerova Marie,
Wang Mengzhe,
Brill Monika S,
Kasparek Petr,
Zhou Xunlei,
AlvarezBolado Gonzalo,
Sedlacek Radislav,
Misgeld Thomas,
Stuchlik Ales,
Perlson Eran,
Balastik Martin
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201948512
Subject(s) - czech , library science , philosophy , computer science , linguistics
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 ( CRMP 2) 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 CRMP 2 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 CRMP 2 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 CRMP 2 mediates Sema3F‐dependent synapse pruning and its dysfunction shares histological and behavioral features of ASD .