TEADs, Yap, Taz, Vgll4s transcription factors control the establishment of Left-Right asymmetry in Zebrafish
- University of Virginia, United States
- CNRS/INSERM/Université de Strasbourg, France
- University of Georgia, United States
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.
Metrics
-
- 3,801
- views
-
- 475
- downloads
-
- 17
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
TEADs, Yap, Taz, Vgll4s transcription factors control the establishment of Left-Right asymmetry in Zebrafish
eLife 8:e45241.
https://doi.org/10.7554/eLife.45241
Further reading
-
- Developmental Biology
The articles in this special issue highlight the diversity and complexity of research into reproductive health, including the need for a better understanding of the fundamental biology of reproduction and for new treatments for a range of reproductive disorders.
-
- Developmental Biology
During the trunk to tail transition the mammalian embryo builds the outlets for the intestinal and urogenital tracts, lays down the primordia for the hindlimb and external genitalia, and switches from the epiblast/primitive streak (PS) to the tail bud as the driver of axial extension. Genetic and molecular data indicate that Tgfbr1 is a key regulator of the trunk to tail transition. Tgfbr1 has been shown to control the switch of the neuromesodermal competent cells from the epiblast to the chordoneural hinge to generate the tail bud. We now show that in mouse embryos Tgfbr1 signaling also controls the remodeling of the lateral plate mesoderm (LPM) and of the embryonic endoderm associated with the trunk to tail transition. In the absence of Tgfbr1, the two LPM layers do not converge at the end of the trunk, extending instead as separate layers until the caudal embryonic extremity, and failing to activate markers of primordia for the hindlimb and external genitalia. The vascular remodeling involving the dorsal aorta and the umbilical artery leading to the connection between embryonic and extraembryonic circulation was also affected in the Tgfbr1 mutant embryos. Similar alterations in the LPM and vascular system were also observed in Isl1 null mutants, indicating that this factor acts in the regulatory cascade downstream of Tgfbr1 in LPM-derived tissues. In addition, in the absence of Tgfbr1 the embryonic endoderm fails to expand to form the endodermal cloaca and to extend posteriorly to generate the tail gut. We present evidence suggesting that the remodeling activity of Tgfbr1 in the LPM and endoderm results from the control of the posterior PS fate after its regression during the trunk to tail transition. Our data, together with previously reported observations, place Tgfbr1 at the top of the regulatory processes controlling the trunk to tail transition.
