AUTHOR=Xue Chang , Liu Xiaohui , Wen Bin , Yang Ruimeng , Gao Shuo , Tao Jiong , Zhou Jun 

TITLE=Zebrafish Vestigial Like Family Member 4b Is Required for Valvulogenesis Through Sequestration of Transcription Factor Myocyte Enhancer Factor 2c

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=7

YEAR=2019

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2019.00277

DOI=10.3389/fcell.2019.00277

ISSN=2296-634X

ABSTRACT=<p>A variety of cardiac transcription factors/cofactors, signaling pathways, and downstream structural genes integrate to form the regulatory hierarchies to ensure proper cardiogenesis in vertebrate. Major interaction proteins of the transcription cofactor vestigial like family member 4 (VGLL4) include myocyte enhancer factor 2 (MEF2) and TEA domain transcription factors (TEAD), both of which play important roles in embryonic cardiac development and in adulthood. In this study, we identified that the deficiency of zebrafish <italic>vgll4b</italic> paralog, a unique family member expressed in developing heart, led to an impaired valve development. Mechanistically, in <italic>vgll4b</italic> mutant embryos the disruption of Vgll4b-Mef2c complex, rather than that of Vgll4b-Tead complex, resulted in an aberrant expression of <italic>krüppel-like factor 2a</italic> (<italic>klf2a</italic>) in endocardium. Such misexpression of <italic>klf2a</italic> eventually evoked the valvulogenesis defects. Our findings suggest that zebrafish Vgll4b plays an important role in modulating the transcription activity of Mef2c on <italic>klf2a</italic> during valve development in a blood-flow-independent manner.</p>