Abstract
The vertebrate heart develops from several progenitor lineages. After early-differentiating first heart field (FHF) progenitors form the linear heart tube, late-differentiating second heart field (SHF) progenitors extend the atrium and ventricle, and form inflow and outflow tracts (IFT/OFT). However, the position and migration of late-differentiating progenitors during heart formation remains unclear. Here, we track zebrafish heart development using transgenics based on the cardiopharyngeal gene tbx1. Live imaging uncovers a tbx1 reporter-expressing cell sheath that continuously disseminates from the lateral plate mesoderm towards the forming heart tube. High-speed imaging and optogenetic lineage tracing corroborates that the zebrafish ventricle forms through continuous addition from the undifferentiated progenitor sheath followed by late-phase accrual of the bulbus arteriosus (BA). FGF inhibition during sheath migration reduces ventricle size and abolishes BA formation, refining the window of FGF action during OFT formation. Our findings consolidate previous end-point analyses and establish zebrafish ventricle formation as a continuous process.
Highlights
The vertebrate heart develops from several progenitor lineages
Genetic lineage tracing has shown that both the distal ventricle and outflow tract (OFT) derive from nkx2.5- and ltbp3reporter-expressing cells24,28. nkx2.5:Kaede-based lineage tracking has indicated that most of the ventricular myocardium is already condensed at the cardiac disk, but whether all these cells migrate with the emerging linear heart tube or stay behind has remained unresolved29. nkx2.5:Kaede further marks a seemingly distinct group of cells posterior and outside of the forming heart tube that contributes myocardial progenitors to the distal ventricle and OFT30; how these cells connect to the other ventricular progenitors remains to be uncovered
Ventral o tp 56, 22 hpf Supplementary Fig. 3), and several head muscle groups (Supplementary Fig. 3), tbx[1] reporter expression and lineage tracing labeled the same structures without the endocardium, but craniofacial cartilage and endoderm derivatives, in line with Tbx[1] as a cardiopharyngeal field (CPF) marker[9] (Fig. 2d, s, Supplementary Figs. 2, 3). These results indicate that the tbx[1] reporter expression domain entails anterior lateral plate mesoderm (ALPM)-derived cells that contribute to cardiac lineages including inflow tract (IFT) and OFT structures
Summary
The vertebrate heart develops from several progenitor lineages. After early-differentiating first heart field (FHF) progenitors form the linear heart tube, late-differentiating second heart field (SHF) progenitors extend the atrium and ventricle, and form inflow and outflow tracts (IFT/OFT). Position-based cell-labeling experiments have mapped BA origins to the medio-central region of the heart-forming ALPM that corresponds to the expression domain of nkx2.5 and gata[423], with the proximal-most part of the BA arising from nkx2.5 reporterexpressing pharyngeal arch 2 mesoderm[29]. These analyses support a model of addition of the majority of latedifferentiating myocardium to the ventricle and BA formation after establishment of the linear heart tube. While these enhancers are sufficient in transgenic reporters, endogenous Tbx[1] expression is redundantly coordinated by additional elements in the vicinity of the locus[42]
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