Disruption ofpdgfraalters endocardial and myocardial fusion during zebrafish cardiac assembly.
Cardiac development in vertebrates is a finely tuned process regulated by a set of conserved signaling pathways. Perturbations of these processes are often associated with congenital cardiac malformations. Platelet-derived growth factor receptor α (PDGFRα) is a highly conserved tyrosine kinase receptor, which is essential for development and organogenesis. Disruption ofPdgfrαfunction in murine models is embryonic lethal due to severe cardiovascular defects, suggesting a role in cardiac development, thus necessitating the use of alternative models to explore its precise function. In this study, we generated a zebrafishpdgframutant line by gene trapping, in which the Pdgfra protein is truncated and fused with mRFP (Pdgfra-mRFP). Our results demonstrate thatpdgframutants have defects in cardiac morphology as a result of abnormal fusion of myocardial precursors. Expression analysis of the developing heart at later stages suggested that Pdgfra-mRFP is expressed in the endocardium. Further examination of the endocardium inpdgframutants revealed defective endocardial migration to the midline, where cardiac fusion eventually occurs. Together, our data suggests thatpdgfrais required for proper medial migration of both endocardial and myocardial precursors, an essential step required for cardiac assembly and development.
Zebrafish Centre for Advanced Drug Discovery & Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada M5B 1T8.|Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5S 1A8.|Collaborative Program in Cardiovascular Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 3E2.
Suzan
S
El-Rass
Department of Stem Cells and Developmental Biology, Cell Science Research Center. Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 16635-148, Iran.
Shahram
S
Eisa-Beygi
Zebrafish Centre for Advanced Drug Discovery & Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada M5B 1T8.
Edbert
E
Khong
Zebrafish Centre for Advanced Drug Discovery & Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada M5B 1T8.
Koroboshka
K
Brand-Arzamendi
Zebrafish Centre for Advanced Drug Discovery & Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada M5B 1T8.|Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5S 1A8.|Collaborative Program in Cardiovascular Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 3E2.
Antonio
A
Mauro
Zebrafish Centre for Advanced Drug Discovery & Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada M5B 1T8.|Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5S 1A8.|Collaborative Program in Cardiovascular Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 3E2.|Department of Medicine & Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
Haibo
H
Zhang
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55902, USA.
Karl J
KJ
Clark
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55902, USA.
Stephen C
SC
Ekker
Zebrafish Centre for Advanced Drug Discovery & Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada M5B 1T8 x.wen@utoronto.ca wenx@smh.ca.|Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5S 1A8.|Collaborative Program in Cardiovascular Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 3E2.|Department of Medicine & Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
Xiao-Yan
http://orcid.org/0000-0001-6728-0025
XY
Wen
Cardiac fusion; Gene trapping; Heart development; Pdgfra; Zebrafish