ZFIN ID: ZDB-PUB-171025-7
Unique developmental trajectories and genetic regulation of ventricular and outflow tract progenitors in the zebrafish second heart field
Paffett-Lugassy, N., Novikov, N., Jeffrey, S., Abrial, M., Guner-Ataman, B., Sakthivel, S., Burns, C.E., Burns, C.G.
Date: 2017
Source: Development (Cambridge, England)   144(24): 4616-4624 (Journal)
Registered Authors: Burns (Erter), Caroline, Burns, Geoff, Paffett-Lugassy, Noelle
Keywords: Cardiac progenitors, Congenital heart disease, Outflow tract, Second heart field, Zebrafish, nkx2.5
MeSH Terms:
  • Animals
  • Branchial Region/metabolism
  • Cell Lineage
  • Cell Movement/physiology
  • Fibroblast Growth Factors/genetics
  • Gene Expression Regulation, Developmental
  • Heart Defects, Congenital/embryology*
  • Heart Ventricles/embryology*
  • Heart Ventricles/metabolism
  • Homeobox Protein Nkx-2.5/biosynthesis
  • Mesoderm/metabolism
  • Myocardium/cytology
  • Myocardium/metabolism
  • Signal Transduction/genetics
  • Stem Cells/cytology*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/biosynthesis
  • Zebrafish Proteins/genetics
PubMed: 29061637 Full text @ Development
During mammalian embryogenesis, cardiac progenitor cells constituting the second heart field (SHF) give rise to the right ventricle and primitive outflow tract (OFT). In zebrafish, previous lineage-tracing and mutant analyses suggested that SHF ventricular and OFT progenitors co-migrate to the arterial pole of the zebrafish heart tube soon after their specification in the nkx2.5+ field of anterior lateral plate mesoderm (ALPM). Using additional prospective lineage tracing, we demonstrate that while SHF ventricular progenitors migrate directly to the arterial pole, OFT progenitors become temporarily sequestered in the mesodermal cores of pharyngeal arch 2 (PA2), where they downregulate nkx2.5 expression. While there, they intermingle with precursors for PA2-derived head muscles (HMs) and hypobranchial artery endothelium, which we demonstrate are co-specified with SHF progenitors in the nkx2.5+ ALPM. Soon after their sequestration in PA2, OFT progenitors migrate to the arterial pole of the heart and differentiate into OFT lineages. Lastly, we demonstrate that SHF ventricular and OFT progenitors exhibit unique sensitivities to a mutation in fgf8a Our data highlight novel aspects of SHF, OFT and HM development in zebrafish that will inform mechanistic interpretations of cardiopharyngeal phenotypes in zebrafish models of human congenital disorders.