TEADs, Yap, Taz, Vgll4s transcription factors control the establishment of Left-Right asymmetry in Zebrafish
Abstract
In many vertebrates, establishment of Left-Right (LR) asymmetry results from the activity of a ciliated organ functioning as the LR Organizer (LRO). While regulation of the formation of this structure by major signaling pathways has been described, the transcriptional control of LRO formation is poorly understood. Using the zebrafish model, we show that the transcription factors and cofactors mediating or regulating the transcriptional outcome of the Hippo signaling pathway play a pivotal role in controlling the expression of genes essential to the formation of the LRO including ligands and receptors of signaling pathways involved in this process and most genes required for motile ciliogenesis. Moreover, the transcription cofactor, Vgll4l regulates epigenetic programming in LRO progenitors by controlling the expression of writers and readers of DNA methylation marks. Altogether, our study uncovers a novel and essential role for the transcriptional effectors and regulators of the Hippo pathway in establishing LR asymmetry.
Data availability
RNA sequencing data that support the findings of this study have been deposited in the Gene Expression Omnibus (GEO) under accession code GSE119623 and are also provided in Supplementary File 1.All data generated or analysed during this study are included in the manuscript and supporting files.Source data for Figure 1, 2, 3, 9 and Figure Supplement 1 are provided in source data 1.
Article and author information
Author details
Funding
Centre National de la Recherche Scientifique
- Christine Thisse
National Institutes of Health (R01GM110092)
- Mary Goll
Institut National de la Santé et de la Recherche Médicale
- Christine Thisse
University of Virginia
- Christine Thisse
National Science Foundation (1455901)
- Bernard Thisse
Centre National de la Recherche Scientifique
- Bernard Thisse
Institut National de la Santé et de la Recherche Médicale
- Bernard Thisse
University of Virginia
- Bernard Thisse
National Institutes of Health (R01GM132131)
- Christine Thisse
National Institutes of Health (R01GM132131)
- Jonathan Fillatre
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendationsin the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All ofthe animals were handled according to approved institutional animal care and use committee(IACUC) protocols (#3661) of the University of Virginia. All surgery was performed under tricain anesthesia and every effort was made to minimize suffering.
Copyright
© 2019, Fillatre et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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