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

Xavier  Caubit; Paolo  Gubellini; Joris  Andrieux; Pierre L.  Roubertoux; Mehdi  Metwaly; Bernard  Jacq; Ahmed  Fatmi; Laurence  Had-Aissouni; Kenneth Y.  Kwan; Pascal  Salin; Michèle  Carlier; Agne  Liedén; Eva  Rudd; Marwan  Shinawi; Catherine  Vincent-Delorme; Jean-Marie  Cuisset; Marie-Pierre  Lemaitre; Abderrehamane  Fatimetou; Bénédicte  Duban; Jean-François  Lemaitre; Adrian S. Woolf; Detlef  Bockenhauer; Dany  Severac; Emeric  Dubois; Ying   Zhu; Nenad  Sestan; Alistair N.  Garratt; Lydia  Kerkerian-Le Goff; Laurent  Fasano

doi:10.1038/ng.3681

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

Xavier Caubit , Paolo Gubellini , Joris Andrieux , Pierre L. Roubertoux , Mehdi Metwaly , Bernard Jacq , Ahmed Fatmi , Laurence Had-Aissouni , Kenneth Y. Kwan , Pascal Salin , Michèle Carlier , Agne Liedén , Eva Rudd , Marwan Shinawi , Catherine Vincent-Delorme , Jean-Marie Cuisset , Marie-Pierre Lemaitre , Abderrehamane Fatimetou , Bénédicte Duban , Jean-François Lemaitre Adrian S. Woolf, Detlef Bockenhauer , Dany Severac , Emeric Dubois, Ying Zhu, Nenad Sestan , Alistair N. Garratt , Lydia Kerkerian-Le Goff , Laurent Fasano

Division of Cell Matrix Biology & Regenerative Medicine (L5)

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Abstract

TSHZ3, which encodes a zinc-finger transcription factor, was recently positioned as a hub gene in a module of the 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 19q12-q13.11, which includes autism spectrum disorder (ASD). In Tshz3-null mice, differentially expressed genes include layer-specific markers of cerebral cortical projection neurons (CPNs), and the human orthologs of these genes are strongly associated with ASD. Furthermore, mice heterozygous for Tshz3 show functional changes at synapses established by CPNs and exhibit core ASD-like behavioral abnormalities. These findings highlight essential roles for Tshz3 in CPN development and function, whose alterations can account for ASD in the newly defined TSHZ3 deletion syndrome.

Original language	English
Pages (from-to)	1359-1369
Journal	Nature Genetics
Volume	48
Early online date	26 Sept 2016
DOIs	https://doi.org/10.1038/ng.3681
Publication status	Published - 2016

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Caubit , X., Gubellini , P., Andrieux , J., Roubertoux , P. L., Metwaly , M., Jacq , B., Fatmi , A., Had-Aissouni , L., Kwan , K. Y., Salin , P., Carlier , M., Liedén , A., Rudd , E., Shinawi , M., Vincent-Delorme , C., Cuisset , J.-M., Lemaitre , M.-P., Fatimetou , A., Duban , B., ... Fasano, L. (2016). TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons. Nature Genetics, 48, 1359-1369. https://doi.org/10.1038/ng.3681

@article{55ef4215854f44a697c4cb6ab22c0699,

title = "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 the 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 19q12-q13.11, which includes autism spectrum disorder (ASD). In Tshz3-null mice, differentially expressed genes include layer-specific markers of cerebral cortical projection neurons (CPNs), and the human orthologs of these genes are strongly associated with ASD. Furthermore, mice heterozygous for Tshz3 show functional changes at synapses established by CPNs and exhibit core ASD-like behavioral abnormalities. These findings highlight essential roles for Tshz3 in CPN development and function, whose alterations can account for ASD in the newly defined TSHZ3 deletion syndrome.",

author = "Xavier Caubit and Paolo Gubellini and Joris Andrieux and Roubertoux, {Pierre L.} and Mehdi Metwaly and Bernard Jacq and Ahmed Fatmi and Laurence Had-Aissouni and Kwan, {Kenneth Y.} and Pascal Salin and Mich{\`e}le Carlier and Agne Lied{\'e}n and Eva Rudd and Marwan Shinawi and Catherine Vincent-Delorme and Jean-Marie Cuisset and Marie-Pierre Lemaitre and Abderrehamane Fatimetou and B{\'e}n{\'e}dicte Duban and Jean-Fran{\c c}ois Lemaitre and Woolf, {Adrian S.} and Detlef Bockenhauer and Dany Severac and Emeric Dubois and Ying Zhu and Nenad Sestan and Garratt, {Alistair N.} and {Kerkerian-Le Goff}, Lydia and Laurent Fasano",

year = "2016",

doi = "10.1038/ng.3681",

language = "English",

volume = "48",

pages = "1359--1369",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

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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 , J-M, Lemaitre , M-P, Fatimetou , A, Duban , B, Lemaitre , J-F, Woolf, AS, Bockenhauer , D, Severac , D, Dubois, E, Zhu, Y, Sestan , N, Garratt , AN, Kerkerian-Le Goff , L & Fasano, L 2016, 'TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons', Nature Genetics, vol. 48, pp. 1359-1369. https://doi.org/10.1038/ng.3681

TY - JOUR

T1 - TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons

AU - Caubit , Xavier

AU - Gubellini , Paolo

AU - Andrieux , Joris

AU - Roubertoux , Pierre L.

AU - Metwaly , Mehdi

AU - Jacq , Bernard

AU - Fatmi , Ahmed

AU - Had-Aissouni , Laurence

AU - Kwan , Kenneth Y.

AU - Salin , Pascal

AU - Carlier , Michèle

AU - Liedén , Agne

AU - Rudd , Eva

AU - Shinawi , Marwan

AU - Vincent-Delorme , Catherine

AU - Cuisset , Jean-Marie

AU - Lemaitre , Marie-Pierre

AU - Fatimetou , Abderrehamane

AU - Duban , Bénédicte

AU - Lemaitre , Jean-François

AU - Woolf, Adrian S.

AU - Bockenhauer , Detlef

AU - Severac , Dany

AU - Dubois, Emeric

AU - Zhu, Ying

AU - Sestan , Nenad

AU - Garratt , Alistair N.

AU - Kerkerian-Le Goff , Lydia

AU - Fasano, Laurent

PY - 2016

Y1 - 2016

N2 - TSHZ3, which encodes a zinc-finger transcription factor, was recently positioned as a hub gene in a module of the 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 19q12-q13.11, which includes autism spectrum disorder (ASD). In Tshz3-null mice, differentially expressed genes include layer-specific markers of cerebral cortical projection neurons (CPNs), and the human orthologs of these genes are strongly associated with ASD. Furthermore, mice heterozygous for Tshz3 show functional changes at synapses established by CPNs and exhibit core ASD-like behavioral abnormalities. These findings highlight essential roles for Tshz3 in CPN development and function, whose alterations can account for ASD in the newly defined TSHZ3 deletion syndrome.

AB - TSHZ3, which encodes a zinc-finger transcription factor, was recently positioned as a hub gene in a module of the 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 19q12-q13.11, which includes autism spectrum disorder (ASD). In Tshz3-null mice, differentially expressed genes include layer-specific markers of cerebral cortical projection neurons (CPNs), and the human orthologs of these genes are strongly associated with ASD. Furthermore, mice heterozygous for Tshz3 show functional changes at synapses established by CPNs and exhibit core ASD-like behavioral abnormalities. These findings highlight essential roles for Tshz3 in CPN development and function, whose alterations can account for ASD in the newly defined TSHZ3 deletion syndrome.

U2 - 10.1038/ng.3681

DO - 10.1038/ng.3681

M3 - Article

SN - 1061-4036

VL - 48

SP - 1359

EP - 1369

JO - Nature Genetics

JF - Nature Genetics

ER -

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

Abstract

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