TY - JOUR
T1 - The autism- and schizophrenia-associated protein CYFIP1 regulates bilateral brain connectivity and behaviour
AU - Domínguez-Iturza, Nuria
AU - Lo, Adrian C.
AU - Shah, Disha
AU - Armendáriz, Marcelo
AU - Vannelli, Anna
AU - Mercaldo, Valentina
AU - Trusel, Massimo
AU - Li, Ka Wan
AU - Gastaldo, Denise
AU - Santos, Ana Rita
AU - Callaerts-Vegh, Zsuzsanna
AU - D'Hooge, Rudi
AU - Mameli, Manuel
AU - Van der Linden, Annemie
AU - Smit, August B.
AU - Achsel, Tilmann
AU - Bagni, Claudia
PY - 2019/8/1
Y1 - 2019/8/1
N2 - Copy-number variants of the CYFIP1 gene in humans have been linked to autism spectrum disorders (ASD) and schizophrenia (SCZ), two neuropsychiatric disorders characterized by defects in brain connectivity. Here, we show that CYFIP1 plays an important role in brain functional connectivity and callosal functions. We find that Cyfip1-heterozygous mice have reduced functional connectivity and defects in white matter architecture, similar to phenotypes found in patients with ASD, SCZ and other neuropsychiatric disorders. Cyfip1-deficient mice also present decreased myelination in the callosal axons, altered presynaptic function, and impaired bilateral connectivity. Finally, Cyfip1 deficiency leads to abnormalities in motor coordination, sensorimotor gating and sensory perception, which are also known neuropsychiatric disorder-related symptoms. These results show that Cyfip1 haploinsufficiency compromises brain connectivity and function, which might explain its genetic association to neuropsychiatric disorders.
AB - Copy-number variants of the CYFIP1 gene in humans have been linked to autism spectrum disorders (ASD) and schizophrenia (SCZ), two neuropsychiatric disorders characterized by defects in brain connectivity. Here, we show that CYFIP1 plays an important role in brain functional connectivity and callosal functions. We find that Cyfip1-heterozygous mice have reduced functional connectivity and defects in white matter architecture, similar to phenotypes found in patients with ASD, SCZ and other neuropsychiatric disorders. Cyfip1-deficient mice also present decreased myelination in the callosal axons, altered presynaptic function, and impaired bilateral connectivity. Finally, Cyfip1 deficiency leads to abnormalities in motor coordination, sensorimotor gating and sensory perception, which are also known neuropsychiatric disorder-related symptoms. These results show that Cyfip1 haploinsufficiency compromises brain connectivity and function, which might explain its genetic association to neuropsychiatric disorders.
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UR - http://www.scopus.com/inward/citedby.url?scp=85070997885&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-11203-y
DO - 10.1038/s41467-019-11203-y
M3 - Article
C2 - 31371726
AN - SCOPUS:85070997885
SN - 2041-1723
VL - 10
SP - 1
EP - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3454
ER -
