Nr2f-dependent allocation of ventricular cardiomyocyte and pharyngeal muscle progenitors

• Published in: PLoS genetics 2019-02, Vol.15 (2), p.e1007962
• Main Authors: Dohn, Tracy E, Ravisankar, Padmapriyadarshini, Tirera, Fouley T, Martin, Kendall E, Gafranek, Jacob T, Duong, Tiffany B, VanDyke, Terri L, Touvron, Melissa, Barske, Lindsey A, Crump, J Gage, Waxman, Joshua S
• Format: Article
• Language: English
• Subjects: Acids; Analysis; Animals; Animals, Genetically Modified; Biology and Life Sciences; Body Patterning - genetics; Cardiomyocytes; Cell Lineage - genetics; COUP Transcription Factor II - genetics; COUP Transcription Factor II - metabolism; Craniofacial Abnormalities - embryology; Craniofacial Abnormalities - genetics; Defects; Developmental biology; Distribution; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Embryonic Stem Cells - cytology; Embryonic Stem Cells - metabolism; Etiology; Funding; Gene mutation; Genetic aspects; Genetic research; Genetic variability; Genetics; Heart; Heart cells; Heart Defects, Congenital - embryology; Heart Defects, Congenital - genetics; Heart Ventricles - cytology; Heart Ventricles - embryology; Heart Ventricles - metabolism; Humans; Medical research; Medicine; Medicine and Health Sciences; Mesoderm; Mesoderm - cytology; Mesoderm - embryology; Mesoderm - metabolism; Models, Animal; Muscle cells; Mutation; Myocytes, Cardiac - cytology; Myocytes, Cardiac - metabolism; Pharyngeal Muscles - cytology; Pharyngeal Muscles - embryology; Pharyngeal Muscles - metabolism; Pharynx; Progenitor cells; Promoter Regions, Genetic; Research and Analysis Methods; Retinoic acid; Signal Transduction; Stem cells; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Tretinoin - metabolism; Ventricle; Vertebrates; Zebrafish; Zebrafish - embryology; Zebrafish - genetics; Zebrafish - metabolism; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1007962

Multiple syndromes share congenital heart and craniofacial muscle defects, indicating there is an intimate relationship between the adjacent cardiac and pharyngeal muscle (PM) progenitor fields. However, mechanisms that direct antagonistic lineage decisions of the cardiac and PM progenitors within the anterior mesoderm of vertebrates are not understood. Here, we identify that retinoic acid (RA) signaling directly promotes the expression of the transcription factor Nr2f1a within the anterior lateral plate mesoderm. Using zebrafish nr2f1a and nr2f2 mutants, we find that Nr2f1a and Nr2f2 have redundant requirements restricting ventricular cardiomyocyte (CM) number and promoting development of the posterior PMs. Cre-mediated genetic lineage tracing in nr2f1a; nr2f2 double mutants reveals that tcf21+ progenitor cells, which can give rise to ventricular CMs and PM, more frequently become ventricular CMs potentially at the expense of posterior PMs in nr2f1a; nr2f2 mutants. Our studies reveal insights into the molecular etiology that may underlie developmental syndromes that share heart, neck and facial defects as well as the phenotypic variability of congenital heart defects associated with NR2F mutations in humans.