CRMP2 mediates Sema3F‐dependent axon pruning and dendritic spine remodeling

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F20%3A00524173" target="_blank" >RIV/67985823:_____/20:00524173 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68378050:_____/20:00524173 RIV/00216208:11310/20:10409280

Výsledek na webu

<a href="https://doi.org/10.15252/embr.201948512" target="_blank" >https://doi.org/10.15252/embr.201948512</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.15252/embr.201948512" target="_blank" >10.15252/embr.201948512</a>

Jazyk výsledku

angličtina

Název v původním jazyce

CRMP2 mediates Sema3F‐dependent axon pruning and dendritic spine remodeling

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

CRMP2 mediates Sema3F‐dependent axon pruning and dendritic spine remodeling

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Embo Reports

ISSN

1469-221X

e-ISSN

—

Svazek periodika

21

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

22

Strana od-do

e48512

Kód UT WoS článku

000519213200020

EID výsledku v databázi Scopus

2-s2.0-85078597836