Premium
pouC Regulates Expression of bmp4 During Atrioventricular Canal Formation in Zebrafish
Author(s) -
Bhakta Minoti,
Padanad Mahesh S.,
Harris John P.,
Lubczyk Christina,
Amatruda James F.,
Munshi Nikhil V.
Publication year - 2019
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.2
Subject(s) - zebrafish , biology , gene knockdown , heart development , atrioventricular canal , homeobox , transcription factor , microbiology and biotechnology , morphogenesis , psychological repression , transcriptional regulation , genetics , heart disease , gene , gene expression , medicine , embryonic stem cell
Background Many human gene mutations have been linked to congenital heart disease (CHD), yet CHD remains a major health issue worldwide due in part to an incomplete understanding of the molecular basis for cardiac malformation. Results Here we identify the orthologous mouse Pou6f1 and zebrafish pouC as POU homeodomain transcription factors enriched in the developing heart. We find that pouC is a multi‐functional transcriptional regulator containing separable activation, repression, protein–protein interaction, and DNA binding domains. Using zebrafish heart development as a model system, we demonstrate that pouC knockdown impairs cardiac morphogenesis and affects cardiovascular function. We also find that levels of pouC expression must be fine‐tuned to enable proper heart formation. At the cellular level, we demonstrate that pouC knockdown disrupts atrioventricular canal (AVC) cardiomyocyte maintenance, although chamber myocyte specification remains intact. Mechanistically, we show that pouC binds a bmp4 intronic regulatory element to mediate transcriptional activation. Conclusions Taken together, our study establishes pouC as a novel transcriptional input into the regulatory hierarchy that drives AVC morphogenesis in zebrafish. We anticipate that these findings will inform future efforts to explore functional conservation in mammals and potential association with atrioventricular septal defects in humans. Developmental Dynamics 248:173‐188, 2019. © 2018 Wiley Periodicals, Inc.