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Molecular Autism
Published in: Molecular Autism 1/2018

Open Access 01-12-2018 | Research

Analysis of the expression pattern of the schizophrenia-risk and intellectual disability gene TCF4 in the developing and adult brain suggests a role in development and plasticity of cortical and hippocampal neurons

Authors: Matthias Jung, Benjamin M. Häberle, Tristan Tschaikowsky, Marie-Theres Wittmann, Elli-Anna Balta, Vivien-Charlott Stadler, Christiane Zweier, Arnd Dörfler, Christian Johannes Gloeckner, D. Chichung Lie

Published in: Molecular Autism | Issue 1/2018

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Abstract

Background

Haploinsufficiency of the class I bHLH transcription factor TCF4 causes Pitt-Hopkins syndrome (PTHS), a severe neurodevelopmental disorder, while common variants in the TCF4 gene have been identified as susceptibility factors for schizophrenia. It remains largely unknown, which brain regions are dependent on TCF4 for their development and function.

Methods

We systematically analyzed the expression pattern of TCF4 in the developing and adult mouse brain. We used immunofluorescent staining to identify candidate regions whose development and function depend on TCF4. In addition, we determined TCF4 expression in the developing rhesus monkey brain and in the developing and adult human brain through analysis of transcriptomic datasets and compared the expression pattern between species. Finally, we morphometrically and histologically analyzed selected brain structures in Tcf4-haploinsufficient mice and compared our morphometric findings to neuroanatomical findings in PTHS patients.

Results

TCF4 is broadly expressed in cortical and subcortical structures in the developing and adult mouse brain. The TCF4 expression pattern was highly similar between humans, rhesus monkeys, and mice. Moreover, Tcf4 haploinsufficiency in mice replicated structural brain anomalies observed in PTHS patients.

Conclusion

Our data suggests that TCF4 is involved in the development and function of multiple brain regions and indicates that its regulation is evolutionary conserved. Moreover, our data validate Tcf4-haploinsufficient mice as a model to study the neurodevelopmental basis of PTHS.
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Metadata
Title
Analysis of the expression pattern of the schizophrenia-risk and intellectual disability gene TCF4 in the developing and adult brain suggests a role in development and plasticity of cortical and hippocampal neurons
Authors
Matthias Jung
Benjamin M. Häberle
Tristan Tschaikowsky
Marie-Theres Wittmann
Elli-Anna Balta
Vivien-Charlott Stadler
Christiane Zweier
Arnd Dörfler
Christian Johannes Gloeckner
D. Chichung Lie
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Molecular Autism / Issue 1/2018
Electronic ISSN: 2040-2392
DOI
https://doi.org/10.1186/s13229-018-0200-1

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