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Latent TGF-β binding protein 3 identifies a second heart field in zebrafish.

Abstract：

:The four-chambered mammalian heart develops from two fields of cardiac progenitor cells distinguished by their spatiotemporal patterns of differentiation and contributions to the definitive heart. The first heart field differentiates earlier in lateral plate mesoderm, generates the linear heart tube and ultimately gives rise to the left ventricle. The second heart field (SHF) differentiates later in pharyngeal mesoderm, elongates the heart tube, and gives rise to the outflow tract and much of the right ventricle. Because hearts in lower vertebrates contain a rudimentary outflow tract but not a right ventricle, the existence and function of SHF-like cells in these species has remained a topic of speculation. Here we provide direct evidence from Cre/Lox-mediated lineage tracing and loss-of-function studies in zebrafish, a lower vertebrate with a single ventricle, that latent TGF-β binding protein 3 (ltbp3) transcripts mark a field of cardiac progenitor cells with defining characteristics of the anterior SHF in mammals. Specifically, ltbp3(+) cells differentiate in pharyngeal mesoderm after formation of the heart tube, elongate the heart tube at the outflow pole, and give rise to three cardiovascular lineages in the outflow tract and myocardium in the distal ventricle. In addition to expressing Ltbp3, a protein that regulates the bioavailability of TGF-β ligands, zebrafish SHF cells co-express nkx2.5, an evolutionarily conserved marker of cardiac progenitor cells in both fields. Embryos devoid of ltbp3 lack the same cardiac structures derived from ltbp3(+) cells due to compromised progenitor proliferation. Furthermore, small-molecule inhibition of TGF-β signalling phenocopies the ltbp3-morphant phenotype whereas expression of a constitutively active TGF-β type I receptor rescues it. Taken together, our findings uncover a requirement for ltbp3-TGF-β signalling during zebrafish SHF development, a process that serves to enlarge the single ventricular chamber in this species.

journal_name

Nature

journal_title

Nature

authors

Zhou Y,Cashman TJ,Nevis KR,Obregon P,Carney SA,Liu Y,Gu A,Mosimann C,Sondalle S,Peterson RE,Heideman W,Burns CE,Burns CG

doi

10.1038/nature10094

subject

Has Abstract

pub_date

2011-05-29 00:00:00

pages

645-8

issue

7353

eissn

0028-0836

issn

1476-4687

pii

nature10094

journal_volume

474

pub_type

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