scRNA sequencing uncovers a TCF4-dependent transcription factor network regulating commissure development in mouse
Wittmann MT, Katada S, Sock E, Kirchner P, Ekici AB, Wegner M, Nakashima K, Lie DC, Reis A (2021)
Publication Language: English
Publication Type: Journal article, Original article
Publication year: 2021
Journal
Book Volume: 148
Article Number: dev196022
Journal Issue: 14
DOI: 10.1242/DEV.196022
Abstract
Transcription factor 4 (TCF4) is a crucial regulator of neurodevelopment and has been linked to the pathogenesis of autism, intellectual disability and schizophrenia. As a class I bHLH transcription factor (TF), it is assumed that TCF4 exerts its neurodevelopmental functions through dimerization with proneural class II bHLH TFs. Here, we aim to identify TF partners of TCF4 in the control of interhemispheric connectivity formation. Using a new bioinformatic strategy integrating TF expression levels and regulon activities from single cell RNA-sequencing data, we find evidence that TCF4 interacts with non-bHLH TFs and modulates their transcriptional activity in Satb2+ intercortical projection neurons. Notably, this network comprises regulators linked to the pathogenesis of neurodevelopmental disorders, e.g. FOXG1, SOX11 and BRG1. In support of the functional interaction of TCF4 with non-bHLH TFs, we find that TCF4 and SOX11 biochemically interact and cooperatively control commissure formation in vivo, and regulate the transcription of genes implicated in this process. In addition to identifying new candidate interactors of TCF4 in neurodevelopment, this study illustrates how scRNA-Seq data can be leveraged to predict TF networks in neurodevelopmental processes.
Authors with CRIS profile
Marie-Theres Wittmann
Lehrstuhl für Humangenetik
Elisabeth Sock
Medizinische Fakultät
Arif Bülent Ekici
Lehrstuhl für Humangenetik
Michael Wegner
Lehrstuhl für Biochemie und Pathobiochemie
Dieter Chichung Lie
Professur für Molekulare Medizin mit dem Schwerpunkt Molekulare Bildgebung
André Wiesmann da Silva Reis
Lehrstuhl für Humangenetik
Related research project(s)
Involved external institutions
Japan (JP)How to cite
APA:
Wittmann, M.-T., Katada, S., Sock, E., Kirchner, P., Ekici, A.B., Wegner, M.,... Reis, A. (2021). scRNA sequencing uncovers a TCF4-dependent transcription factor network regulating commissure development in mouse. Development, 148(14). https://dx.doi.org/10.1242/DEV.196022
MLA:
Wittmann, Marie-Theres, et al. "scRNA sequencing uncovers a TCF4-dependent transcription factor network regulating commissure development in mouse." Development 148.14 (2021).
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