Zebrafish mutants and TEAD reporters reveal essential functions for Yap and Taz in posterior cardinal vein development

Scientific Reports. 2018;8(1):1-15 DOI 10.1038/s41598-018-27657-x

 

Journal Homepage

Journal Title: Scientific Reports

ISSN: 2045-2322 (Online)

Publisher: Nature Publishing Group

LCC Subject Category: Medicine | Science

Country of publisher: United Kingdom

Language of fulltext: English

Full-text formats available: PDF, HTML

 

AUTHORS


Matteo Astone (University of Padova, Department of Biology)

Jason Kuan Han Lai (Max Planck Institute for Heart and Lung Research)

Sirio Dupont (University of Padova, Department of Molecular Medicine)

Didier Y. R. Stainier (Max Planck Institute for Heart and Lung Research)

Francesco Argenton (University of Padova, Department of Biology)

Andrea Vettori (University of Padova, Department of Biology)

EDITORIAL INFORMATION

Blind peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 20 weeks

 

Abstract | Full Text

Abstract As effectors of the Hippo signaling cascade, YAP1 and TAZ are transcriptional regulators playing important roles in development, tissue homeostasis and cancer. A number of different cues, including mechanotransduction of extracellular stimuli, adhesion molecules, oncogenic signaling and metabolism modulate YAP1/TAZ nucleo-cytoplasmic shuttling. In the nucleus, YAP1/TAZ tether with the DNA binding proteins TEADs, to activate the expression of target genes that regulate proliferation, migration, cell plasticity, and cell fate. Based on responsive elements present in the human and zebrafish promoters of the YAP1/TAZ target gene CTGF, we established zebrafish fluorescent transgenic reporter lines of Yap1/Taz activity. These reporter lines provide an in vivo view of Yap1/Taz activity during development and adulthood at the whole organism level. Transgene expression was detected in many larval tissues including the otic vesicles, heart, pharyngeal arches, muscles and brain and is prominent in endothelial cells. Analysis of vascular development in yap1/taz zebrafish mutants revealed specific defects in posterior cardinal vein (PCV) formation, with altered expression of arterial/venous markers. The overactivation of Yap1/Taz in endothelial cells was sufficient to promote an aberrant vessel sprouting phenotype. Our findings confirm and extend the emerging role of Yap1/Taz in vascular development including angiogenesis.