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.
Publications
Three putative murine Teashirt orthologues specify trunk structures in Drosophila in the same way as the Drosophila teashirt gene
Substrate stiffness alters layer architecture and biophysics of human induced pluripotent stem cells to modulate their differentiation potential
Maintenance of antioxidant defenses of brain cells: plasma membrane glutamate transporters and beyond.
Toward a new role for plasma membrane sodium-dependent glutamate transporters of astrocytes: maintenance of antioxidant defenses beyond extracellular glutamate clearance.
Teashirt 3 regulates development of neurons involved in both respiratory rhythm and airflow control.
Three putative murine Teashirt orthologues specify trunk structures in Drosophila in the same way as the Drosophila teashirt gene
News
A touch of softness to facilitate differentiation of human induced pluripotent stem cells
Tuning of substrate stiffness enhances mesendoderm/endoderm hiPSC differentiation by modifying their epithelial properties.
Targeted Tshz3 deletion in corticostriatal circuit components segregates core autistic behaviors
Nos résultats apportent un éclairage nouveau sur l’implication du circuit corticostrié dans les TSA.
Data published in Hum Mol Genet. confirm that Tshz3 heterozygous mice constitute a model that replicates many of the clinical problems reported in patients with TSHZ3 heterozygous conditions.
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