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

Jung M, Häberle B, Tschaikowsky T, Wittmann MT, Balta EA, Stadler VC, Zweier C, Dörfler A, Gloeckner CJ, Lie DC (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Molecular Autism BioMed Central

Book Volume: 9

DOI: 10.1186/s13229-018-0200-1

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.

Authors with CRIS profile

Matthias Jung Professur für Molekulare Medizin mit dem Schwerpunkt Molekulare Bildgebung Benjamin Häberle Professur für Molekulare Medizin mit dem Schwerpunkt Molekulare Bildgebung Tristan Tschaikowsky Professur für Molekulare Medizin mit dem Schwerpunkt Molekulare Bildgebung Marie-Theres Wittmann Lehrstuhl für Humangenetik Elli-Anna Balta Lehrstuhl für Biochemie und Pathobiochemie Christiane Zweier Medizinische Fakultät Arnd Dörfler Department of Neuroradiology Dieter Chichung Lie Institut für Biochemie

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Involved external institutions

Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) DE Germany (DE)

How to cite

APA:

Jung, M., Häberle, B., Tschaikowsky, T., Wittmann, M.-T., Balta, E.-A., Stadler, V.-C.,... Lie, D.C. (2018). 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. Molecular Autism , 9. https://doi.org/10.1186/s13229-018-0200-1

MLA:

Jung, Matthias, et al. "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." Molecular Autism 9 (2018).

BibTeX: Download