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, mice heterozygous for Tshz3 deletion 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.

Differential Brain, Cognitive and Motor Profiles Associated with Partial Trisomy. Modeling Down Syndrome in Mice

“…We controlled mice for visual, auditory and pain perception according to the protocols previously presented (Caubit et al 2016 ).…”

TIAM2S as a novel regulator for serotonin level enhances brain plasticity and locomotion behavior

“…In addition, genomic structural variants of human TIAM2 at intron 1 (chr6 155438256) or intron 4 (chr6 155463366) with Alu mobile‐element insertions is associated with autism spectrum disorders, which are neurodevelopmental disorders with typical impairment in communication, aberrant social interaction, and restrictive patterns of behaviors. Furthermore, the expression profile of TIAM2 is the highest correlated with TSHZ3 (a zinc‐finger transcription factor), the dysfunction of which contributes to nervous system pathologies of autism spectrum disorders, in the developing neocortex . These studies demonstrate that TIAM2 may be associated with the risk and pathogenesis of neurodevelopmental disorders.…”

“…Furthermore, the expression profile of TIAM2 is the highest correlated with TSHZ3 (a zinc-finger transcription factor), the dysfunction of which contributes to nervous system pathologies of autism spectrum disorders, in the developing neocortex. 56 These studies demonstrate that TIAM2 may be associated with the risk and pathogenesis of neurodevelopmental disorders.…”

MicroRNA-125b-1-3p mediates intervertebral disc degeneration in rats by targeting teashirt zinc finger homeobox 3

“…The human genome contains at ≥178 homeobox sequences, among which 160 genes may be translated into homeodomains within functional proteins (18). Teashirt zinc finger homeobox 3 (TSHZ3) encodes a zinc-finger transcription factor and is highly expressed in the developing human neocortex (19). TSHZ3 also serves a primary role in smooth muscle formation (20) but its specific functions remain ambiguous.…”