TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons

Xavier Caubit, Paolo Gubellini, Joris Andrieux, Pierre L. Roubertoux, Mehdi Metwaly, Bernard Jacq, Ahmed Fatmi, Laurence Had-Aissouni, Kenneth Y. Kwan, Pascal Salin, Michèle Carlier, Agne Liedén, Eva Rudd, Marwan Shinawi, Catherine Vincent-Delorme, Jean Marie Cuisset, Marie Pierre Lemaitre, Fatimetou Abderrehamane, Bénédicte Duban, Jean François LemaitreAdrian S. Woolf, Detlef Bockenhauer, Dany Severac, Emeric Dubois, Ying Zhu, Nenad Sestan, Alistair N. Garratt, Lydia Kerkerian-Le Goff, Laurent Fasano

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1359-1369
Number of pages11
JournalNature Genetics
Volume48
Issue number11
DOIs
StatePublished - Nov 1 2016

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