An international consortium of scientists and clinicians around teams of Laurent Fasano and Lydia Kerkerian-Le Goff reveal a link between loss of function of the gene ‘Teashirt’ (TSHZ3), defects in cortical neurons and autistic syndrome.

In a paper to be published in the journal Nature Genetics1, the teams of Laurent Fasano and Lydia Kerkerian-Le Goff, in collaboration with Pierre Roubertoux (“Medical Genetics and Functional Genomics” Unit, Aix-Marseille University / INSERM UMR S910), Joris Andrieux (Medical Genetics Institute, Jeanne Hospital de Flandre, CHRU Lille, France) and several European and American laboratories, identify TSHZ3 as a new gene linked to austim spectrum disorder (ASD).

The gene TSHZ3 had already been implicated by Laurent Fasano’s team as being essential for the development of the ureteral smooth muscle and of neuronal circuits critical for the acquisition of breathing. In the article to be published in Nature Genetics, the international research consortium shows, in human and in mouse models, the existence of a direct link between TSHZ3/Tshz3 deletion and a subtype of ASD, characterized by the association of autistic traits and congenital abnormalities of the urinary tract. In the cerebral cortex of Tshz3-null mice, differentially expressed genes include specific markers of deep layer projection neurons, and a majority of the human orthologs of these genes are linked to ASD. The Tshz3 heterozygous mice display autistic-like behaviours as well as alterations in the transmission and plasticity at synapses established by the cortical deep layer projection neurons, supporting a link between ASD and defects in synapse formation and/or function. The coexistence of autistic traits and of renal tract defects associated with the loss of function of TSHZ3 could guide the early diagnosis and management of patients with this subtype of ASD.

TSHZ3-expressing neurons (red) are located in deep layers (L) 5 and L6 of the cerebral cortex; coronal brain sections of the mouse cortex at E18.5.

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

Caubit X, Gubellini P, Andrieux J, Roubertoux PL, Metwaly M, Jacq B, Fatmi A, Had-Aissouni L, Kwan KY, Salin P, Carlier M, Liedén A, Rudd E, Shinawi M, Vincent-Delorme C, Cuisset JM, Lemaitre MP, Abderrehamane F, Duban B, Lemaitre JF, Woolf AS, Bockenhauer D, Severac D, Dubois E, Zhu Y, Sestan N, Garratt AN, Kerkerian-Le Goff L, Fasano L. Nat Genet. 2016 Sep 26. doi: 10.1038/ng.3681. [Epub ahead of print]. PMID: 27668656

Contact : laurent.fasano@univ-amu.fr; lydia.kerkerian-le-goff@univ-amu.fr