PUBLICATION
pouC regulates expression of bmp4 during atrioventricular canal formation in zebrafish
- Authors
- Bhakta, M., Padanad, M.S., Harris, J.P., Lubczyk, C., Amatruda, J.F., Munshi, N.V.
- ID
- ZDB-PUB-181118-6
- Date
- 2018
- Source
- Developmental Dynamics : an official publication of the American Association of Anatomists 248(2): 173-188 (Journal)
- Registered Authors
- Amatruda, James F., Padanad, Mahesh
- Keywords
- Atrioventricular canal, Cardiac development, Morphogenesis, Transcription factor, pouC
- MeSH Terms
-
- Animals
- Bone Morphogenetic Protein 4/genetics*
- Bone Morphogenetic Protein 4/metabolism
- Gene Expression Regulation, Developmental*
- Heart/embryology
- Heart/growth & development
- Heart Septal Defects
- Heart Septum/embryology
- Heart Septum/growth & development*
- Mice
- POU Domain Factors/metabolism
- POU Domain Factors/physiology*
- Protein Binding
- Transcription Factors
- Zebrafish
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- Zebrafish Proteins/physiology*
- PubMed
- 30444277 Full text @ Dev. Dyn.
Citation
Bhakta, M., Padanad, M.S., Harris, J.P., Lubczyk, C., Amatruda, J.F., Munshi, N.V. (2018) pouC regulates expression of bmp4 during atrioventricular canal formation in zebrafish. Developmental Dynamics : an official publication of the American Association of Anatomists. 248(2):173-188.
Abstract
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 (AVSDs) in humans. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping