TY - JOUR
T1 - TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons
AU - Caubit, Xavier
AU - Gubellini, Paolo
AU - Andrieux, Joris
AU - Roubertoux, Pierre L.
AU - Metwaly, Mehdi
AU - Jacq, Bernard
AU - Fatmi, Ahmed
AU - Had-Aissouni, Laurence
AU - Kwan, Kenneth Y.
AU - Salin, Pascal
AU - Carlier, Michèle
AU - Liedén, Agne
AU - Rudd, Eva
AU - Shinawi, Marwan
AU - Vincent-Delorme, Catherine
AU - Cuisset, Jean Marie
AU - Lemaitre, Marie Pierre
AU - Abderrehamane, Fatimetou
AU - Duban, Bénédicte
AU - Lemaitre, Jean François
AU - Woolf, Adrian S.
AU - Bockenhauer, Detlef
AU - Severac, Dany
AU - Dubois, Emeric
AU - Zhu, Ying
AU - Sestan, Nenad
AU - Garratt, Alistair N.
AU - Kerkerian-Le Goff, Lydia
AU - Fasano, Laurent
N1 - Funding Information:
We thank M. Galdi, V. Vanoosten and C. Scajola who assisted with behavioral testing. This work was supported by funding from CNRS and Aix-Marseille University to L.K.-L.G., L.F. and M.C.; INSERM and Aix-Marseille University to P.L.R.; Fédération pour la Recherche sur le Cerveau (FRC) to L.F.; National Institutes of Health grants MH103339, MH106934 and MH106874, the Simons Foundation and the Kavli Foundation to N.S.; and the Medical Research Council (MR/L002744/1), the Manchester Biomedical Research Centre and the NIHR Greater Manchester Clinical Research Network to A.S.W. Funding for A.N.G. was provided by a grant from the German Federal Ministry for Education and Research (BMBF, NGFN-plus, 'Alzheimer Disease Integrative Genomics', PNA-01GS08127-3a). Microscopy was performed at the imaging platform of IBDM, supported by the French National Research Agency through the 'Investments for the Future' program (France-BioImaging, ANR-10-INSB-04-01).
Publisher Copyright:
© 2016 Nature America, Inc., part of Springer Nature. All rights reserved.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - TSHZ3, which encodes a zinc-finger transcription factor, was recently positioned as a hub gene in a module of the genes with the highest expression in the developing human neocortex, but its functions remained unknown. Here we identify TSHZ3 as the critical region for a syndrome associated with heterozygous deletions at 19q12-q13.11, which includes autism spectrum disorder (ASD). In Tshz3-null mice, differentially expressed genes include layer-specific markers of cerebral cortical projection neurons (CPNs), and the human orthologs of these genes are strongly associated with ASD. Furthermore, mice heterozygous for Tshz3 show functional changes at synapses established by CPNs and exhibit core ASD-like behavioral abnormalities. These findings highlight essential roles for Tshz3 in CPN development and function, whose alterations can account for ASD in the newly defined TSHZ3 deletion syndrome.
AB - TSHZ3, which encodes a zinc-finger transcription factor, was recently positioned as a hub gene in a module of the genes with the highest expression in the developing human neocortex, but its functions remained unknown. Here we identify TSHZ3 as the critical region for a syndrome associated with heterozygous deletions at 19q12-q13.11, which includes autism spectrum disorder (ASD). In Tshz3-null mice, differentially expressed genes include layer-specific markers of cerebral cortical projection neurons (CPNs), and the human orthologs of these genes are strongly associated with ASD. Furthermore, mice heterozygous for Tshz3 show functional changes at synapses established by CPNs and exhibit core ASD-like behavioral abnormalities. These findings highlight essential roles for Tshz3 in CPN development and function, whose alterations can account for ASD in the newly defined TSHZ3 deletion syndrome.
UR - http://www.scopus.com/inward/record.url?scp=84988708762&partnerID=8YFLogxK
U2 - 10.1038/ng.3681
DO - 10.1038/ng.3681
M3 - Article
C2 - 27668656
AN - SCOPUS:84988708762
SN - 1061-4036
VL - 48
SP - 1359
EP - 1369
JO - Nature Genetics
JF - Nature Genetics
IS - 11
ER -