Unique developmental trajectories and genetic regulation of ventricular and outflow tract progenitors in the zebrafish second heart field

TY - JOUR

T1 - Unique developmental trajectories and genetic regulation of ventricular and outflow tract progenitors in the zebrafish second heart field

AU - Paffett-Lugassy, Noelle

AU - Novikov, Natasha

AU - Jeffrey, Spencer

AU - Abrial, Maryline

AU - Guner-Ataman, Burcu

AU - Sakthivel, Srinivasan

AU - Burns, Caroline E.

AU - Burns, C. Geoffrey

PY - 2017/12

Y1 - 2017/12

N2 - 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.

AB - 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.

KW - Cardiac progenitors

KW - Congenital heart disease

KW - Nkx2.5

KW - Outflow tract

KW - Second heart field

KW - Zebrafish

U2 - 10.1242/dev.153411

DO - 10.1242/dev.153411

M3 - Journal article

C2 - 29061637

AN - SCOPUS:85038446589

SN - 0950-1991

VL - 144

SP - 4616

EP - 4624

JO - Development

JF - Development

IS - 24

ER -