TEAM
Transcriptional regulatory networks in development and diseases
Group leader : L. Fasano
Our laboratory aims to understand the mechanisms that control normal development and how their deregulation causes disease, with a particular interest in autism spectrum disorders.
FOR BEGINNERS
Our laboratory aims to understand the mechanisms that control normal development and how their deregulation causes disease, with a particular interest in autism spectrum disorders (ASD).
ASD is a heterogeneous group of neurodevelopmental pathologies characterized by impairments in social interaction and stereotypies. Although the rates of ASD diagnosis are increasing, there is no treatments for the core ASD symptoms. New therapeutic strategies to improve them are thus needed.
We previously linked the human TSHZ3 gene to a new ASD syndrome (19q12DS) and elucidated some of its molecular, cellular and synaptic mechanisms by using different Tshz3 mouse models. This initial work points to cortical and corticostriatal circuitry dysfunctions in TSHZ3-related ASD, and identifies the early postnatal period of cortical development as a critical phase for this pathology.
Our main objective is to gain more knowledge onto “where” and “when” Tshz3 is essential for the development and function of the corticostriatal circuitry in relationship with ASD, as basis for the research of novel treatment strategies. To do so, we are characterizing new Tshz3 mouse models.

Our paper in Biological Psychiatry (Postnatal Tshz3 deletion drives altered corticostriatal function and ASD-like behavior) links postnatal loss of Tshz3 gene and Autism Spectrum Disorder.
FOR SPECIALISTS
Our laboratory aims to understand the mechanisms that control normal development and how their deregulation causes disease, with a particular interest in autism spectrum disorders (ASD).
ASD is a heterogeneous group of neurodevelopmental pathologies characterized by impairments in social interaction and stereotypies. Although the rates of ASD diagnosis are increasing, there is no treatments for the core ASD symptoms. New therapeutic strategies to improve them are thus needed.
We previously linked the human TSHZ3 gene to a new ASD syndrome (19q12DS) and elucidated some of its molecular, cellular and synaptic mechanisms by using different Tshz3 mouse models. In these models, heterozygous (Tshz3+/lacZ model) and postnatal (Camk2a-cKO model) deletion of Tshz3 in the brain leads to ASD-like phenotype, namely impaired social behavior and stereotypies, paralleled with impaired transmission and plasticity at corticostriatal synapses. This initial work points to cortical and corticostriatal circuitry dysfunctions in TSHZ3-related ASD, and identifies the early postnatal period of cortical development as a critical phase for this pathology.

On our publication in Nature Genetics we identified a module of genes co-expressed with TSHZ3 in the human neocortex at mid gestation, which is enriched for ASD-associated genes (blue “balls”).
A major goal is to better understand how deletion of the TSHZ3 gene leads to the appearance of the ASD core symptoms. To address this question, our team developed mouse models allowing targeted conditional deletion of Tshz3. We use this strategy to delete Tshz3 in two components of the corticostriatal circuitry: the cortical projection neurons (CPNs) and the striatal cholinergic interneurons (SCINs).
We also generated a conditional rescue mouse model to determine whether the timely-controlled restoration of Tshz3 expression in CPNs and/or SCINs can improve ASD symptoms. This approach was stimulated by the fact that the viability of Tshz3 mutant neurons is not affected incorticostriatal circuits, raising the promising issue of rescuing postnatally the ASD phenotype. We are characterizing this conditional rescue mouse model.

TSHZ3 protein (red) is expressed at high levels by cortical projection neurons in deep-layer of the mouse cerebral cortex.
Selected publications
PUBLICATION
March 15th, 2022
Targeted Tshz3 deletion in corticostriatal circuit components segregates core autistic behaviors
PUBLICATION
April 20th, 2018
Regulation of the positive transcriptional effect of PLZF through a non-canonical EZH2 activity
PUBLICATION
September 26th, 2016
TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons.
PUBLICATION
February 21st, 2013
The tiptop/teashirt genes regulate cell differentiation and renal physiology in Drosophila.
PUBLICATION
July 14th, 2010
Teashirt 3 regulates development of neurons involved in both respiratory rhythm and airflow control.
PUBLICATION
October 1st, 2008
Teashirt 3 is necessary for ureteral smooth muscle differentiation downstream of SHH and BMP4.
PUBLICATION
July 15th, 2005
A critical role of teashirt for patterning the ventral epidermis is masked by ectopic expression of tiptop, a paralog of teashirt in Drosophila.
PUBLICATION
May 23rd, 2005
Expression patterns of the three Teashirt-related genes define specific boundaries in the developing and postnatal mouse forebrain.
PUBLICATION
March 1st, 2004
Three putative murine Teashirt orthologues specify trunk structures in Drosophila in the same way as the Drosophila teashirt gene.
PUBLICATION
March 1st, 2000
Vertebrate orthologues of the Drosophila region-specific patterning gene teashirt.
PUBLICATION
January 11th, 1991
The gene teashirt is required for the development of Drosophila embryonic trunk segments and encodes a protein with widely spaced zinc finger motifs.
PUBLICATION
May 6th, 2013
TSHZ3 and SOX9 Regulate the Timing of Smooth Muscle Cell Differentiation in the Ureter by Reducing Myocardin Activity.
PUBLICATION
August 1st, 2012
Tandem duplication of chromosomal segments is common in ovarian and breast cancer genomes.
PUBLICATION
March 23rd, 2012
Teashirt in cell proliferation
PUBLICATION
January 1st, 2012
Toward a new role for plasma membrane sodium-dependent glutamate transporters of astrocytes: maintenance of antioxidant defenses beyond extracellular glutamate clearance.
PUBLICATION
January 1st, 2012
Maintenance of antioxidant defenses of brain cells: plasma membrane glutamate transporters and beyond.
PUBLICATION
July 14th, 2011
Oxidative stress and prevention of the adaptive response to chronic iron overload in the brain of young adult rats exposed to a 150 kilohertz electromagnetic field.
PUBLICATION
July 1st, 2011
Teashirt-3, a novel regulator of muscle differentiation, associates with BRG1-associated factor 57 (BAF57) to inhibit myogenin gene expression.
PUBLICATION
January 1st, 2010
Ureter myogenesis: putting Teashirt into context.
PUBLICATION
January 1st, 2010
Analysis of TSHZ2 and TSHZ3 genes in congenital pelvi-ureteric junction obstruction.
PUBLICATION
August 15th, 2007
Tshz1 is required for axial skeleton, soft palate and middle ear development in mice.
PUBLICATION
July 1st, 2007
Direct interaction between Teashirt and Sex combs reduced proteins, via Tsh's acidic domain, is essential for specifying the identity of the prothorax in Drosophila.
PUBLICATION
October 1st, 2006
Teashirt 3 expression in the chick embryo reveals a remarkable association with tendon development.
PUBLICATION
August 8th, 2006
Chaetognath phylogenomics: a protostome with deuterostome-like development.
PUBLICATION
July 1st, 2005
Restricted expression of a median Hox gene in the central nervous system of chaetognaths.
PUBLICATION
April 1st, 2003
Hox gene survey in the chaetognath Spadella cephaloptera: evolutionary implications.
PUBLICATION
June 12th, 2002
Characterisation of set-1, a conserved PR/SET domain gene in Caenorhabditis elegans.
PUBLICATION
March 1st, 2002
Grunge, related to human Atrophin-like proteins, has multiple functions in Drosophila development.
PUBLICATION
January 1st, 2002
Cubitus interruptus acts to specify naked cuticle in the trunk of Drosophila embryos.
PUBLICATION
January 1st, 2000
Characterization of the two zebrafish orthologues of the KAL-1 gene underlying X chromosome-linked Kallmann syndrome.
PUBLICATION
November 15th, 1999
The role of Teashirt in proximal leg development in Drosophila: ectopic Teashirt expression reveals different cell behaviours in ventral and dorsal domains.
PUBLICATION
November 1st, 1999
The levels of the bancal product, a Drosophila homologue of vertebrate hnRNP K protein, affect cell proliferation and apoptosis in imaginal disc cells.
PUBLICATION
April 15th, 1999
The C-terminal domain of armadillo binds to hypophosphorylated teashirt to modulate wingless signalling in Drosophila.
PUBLICATION
July 30th, 1998
Trunk-specific modulation of wingless signalling in Drosophila by teashirt binding to armadillo.
PUBLICATION
November 1st, 1997
Transcriptional regulation of the Drosophila homeotic gene teashirt by the homeodomain protein Fushi tarazu.
PUBLICATION
January 1st, 1997
GIF-DB, a WWW database on gene interactions involved in Drosophila melanogaster development.
PUBLICATION
October 10th, 1996
The Drosophila teashirt homeotic protein is a DNA-binding protein and modulo, a HOM-C regulated modifier of variegation, is a likely candidate for being a direct target gene.
PUBLICATION
October 1st, 1988