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; Fatimetou Abderrehamane; 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, Fatimetou Abderrehamane, Bénédicte Duban, Jean François LemaitreAdrian S. Woolf, Detlef Bockenhauer, Dany Severac, Emeric Dubois, Ying Zhu, Nenad Sestan, Alistair N. Garratt, Lydia Kerkerian-Le Goff, Laurent Fasano

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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
Number of pages	11
Journal	Nature Genetics
Volume	48
Issue number	11
DOIs	https://doi.org/10.1038/ng.3681
State	Published - Nov 1 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., Abderrehamane, F., Duban, B., ... Fasano, L. (2016). TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons. Nature Genetics, 48(11), 1359-1369. https://doi.org/10.1038/ng.3681

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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 Cuisset, {Jean Marie} and Lemaitre, {Marie Pierre} and Fatimetou Abderrehamane and B{\'e}n{\'e}dicte Duban and Lemaitre, {Jean Fran{\c c}ois} 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",

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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, 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 2016, 'TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons', Nature Genetics, vol. 48, no. 11, pp. 1359-1369. https://doi.org/10.1038/ng.3681

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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 - Abderrehamane, Fatimetou

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 - 2016/11/1

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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.

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U2 - 10.1038/ng.3681

DO - 10.1038/ng.3681

M3 - Article

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AN - SCOPUS:84988708762

SN - 1061-4036

VL - 48

SP - 1359

EP - 1369

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -

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

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