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

ABSTRACT: TSHZ3, which encodes a zinc-finger transcription factor, was recently positioned as a hub gene in a module of 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 19q12q13.11, which includes autism spectrum disorder (ASD). In Tshz3 null mice, differentially expressed genes include layer-specific markers of cerebral cortical projection neurons (CPNs) and their human orthologues are strongly associated with ASD. Furthermore, heterozygous Tshz3-deficient mice show functional changes at synapses established by CPNs and exhibit core ASD-like behavioral abnormalities. These findings reveal essential roles for Tshz3 in CPN development and function, whose alterations can account for ASD in the newly-defined TSHZ3 deletion syndrome.

ORGANISM(S): Mus musculus

PROVIDER: GSE85512 | GEO | 2016/09/26

SECONDARY ACCESSION(S): PRJNA338690

REPOSITORIES: GEO

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Consequences of postnatal Tshz3 deletion: implications for autism spectrum disorder

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