TEADs, Yap, Taz, Vgll4s transcription factors control the establishment of Left-Right asymmetry in zebrafish

Author:

Fillatre Jonathan1,Fauny Jean-Daniel23,Fels Jasmine Alexandra1,Li Cheng4,Goll Mary4ORCID,Thisse Christine12,Thisse Bernard12ORCID

Affiliation:

1. Department of Cell Biology, University of Virginia, Charlottesville, United States

2. Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université de Strasbourg, Illkirch-Graffenstaden, France

3. Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France

4. Department of Genetics, University of Georgia, Athens, 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.

Funder

Centre National de la Recherche Scientifique

Institut National de la Santé et de la Recherche Médicale

University of Virginia

National Science Foundation

National Institutes of Health

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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