Team members

Transcriptional regulatory networks in development and diseases

Our laboratory aims to understand the mechanisms that control normal development and how their deregulation causes disease, with a particular interest in the 19q12 deletion syndrome characterized by congenital malformations of the renal tract and autism spectrum disorder, which are associated to the haploinsufficiency of the gene TSHZ3.

Our laboratory aims to understand the mechanisms that control normal development and how their deregulation causes disease. We have identified a new chromosome 19q12 deletion syndrome (19q12DS). This syndrome is a rare genetic disease caused by the absence of one copy of the TSHZ3 gene. The most common symptoms in people with 19q12DS are congenital malformations of the renal tract (CAKUT) and autism spectrum disorder (ASD). ASD results from neurodevelopmental abnormalities. It is characterized by deficits in social interaction and restricted and repetitive behavior, interests or activities. The diagnosis of autism is primarily clinical and based on behavioral observations. To date, there is no treatment for ASD. As the pathophysiology of ASD is complex, we generated mice lacking one copy of the Tshz3 gene to model the syndrome. Characterization of these mice confirmed the presence of deficits in social interaction and repetitive behaviors and restricted fields of interest, as well as abnormalities of the urinary tract. Our main objective is to gain more knowledge about “where, when and how” the Tshz3 gene is essential for the development and function of certain neural circuits and the renal tract as a basis for the search for new treatment strategies.

To this end, we are performing a detailed molecular, cellular and behavioral characterization of new Tshz3 mouse models. This approach already led to the discovery that 1) postnatal deletion of Tshz3 in mice results in deficits in social interaction and repetitive behaviors and 2) the loss of function of Tshz3 in cortical projection neurons is responsible for social interaction deficits, whereas its loss in cholinergic interneurons in the striatum produces repetitive behavior.

TSHZ3 (red) and CHAT (green) positive striatal cholinergic interneurons

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Alumni

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Elise Arbeille
MCU – AMU, IBDM
Irene Sanchez-Martin
Post-doc at Icahn School of Medicine at Mount Sinai, NY, USA
Teddy Fauquier
Engineer, Marseille Medical Genetics UMR_S910, Marseille France

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