title: Zebrafish second heart field development relies on progenitor specification in anterior lateral plate mesoderm and nkx2.5 function.
abstract: Second heart field (SHF) progenitors perform essential functions during mammalian cardiogenesis. We recently identified a population of cardiac progenitor cells (CPCs) in zebrafish expressing latent TGFβ-binding protein 3 (ltbp3) that exhibits several defining characteristics of the anterior SHF in mammals. However, ltbp3 transcripts are conspicuously absent in anterior lateral plate mesoderm (ALPM), where SHF progenitors are specified in higher vertebrates. Instead, ltbp3 expression initiates at the arterial pole of the developing heart tube. Because the mechanisms of cardiac development are conserved evolutionarily, we hypothesized that zebrafish SHF specification also occurs in the ALPM. To test this hypothesis, we Cre/loxP lineage traced gata4(+) and nkx2.5(+) ALPM populations predicted to contain SHF progenitors, based on evolutionary conservation of ALPM patterning. Traced cells were identified in SHF-derived distal ventricular myocardium and in three lineages in the outflow tract (OFT). We confirmed the extent of contributions made by ALPM nkx2.5(+) cells using Kaede photoconversion. Taken together, these data demonstrate that, as in higher vertebrates, zebrafish SHF progenitors are specified within the ALPM and express nkx2.5. Furthermore, we tested the hypothesis that Nkx2.5 plays a conserved and essential role during zebrafish SHF development. Embryos injected with an nkx2.5 morpholino exhibited SHF phenotypes caused by compromised progenitor cell proliferation. Co-injecting low doses of nkx2.5 and ltbp3 morpholinos revealed a genetic interaction between these factors. Taken together, our data highlight two conserved features of zebrafish SHF development, reveal a novel genetic relationship between nkx2.5 and ltbp3, and underscore the utility of this model organism for deciphering SHF biology.
authors: Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA 02129, USA.
authors: Burcu
authors: B
authors: Guner-Ataman
authors: Noelle
authors: N
authors: Paffett-Lugassy
authors: Meghan S
authors: MS
authors: Adams
authors: Kathleen R
authors: KR
authors: Nevis
authors: Leila
authors: L
authors: Jahangiri
authors: Pablo
authors: P
authors: Obregon
authors: Kazu
authors: K
authors: Kikuchi
authors: Kenneth D
authors: KD
authors: Poss
authors: Caroline E
authors: CE
authors: Burns
authors: C Geoffrey
authors: CG
authors: Burns
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology; D004625:Embryo, Nonmammalian; D004843:Epistasis, Genetic / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006321:Heart / Q000196:embryology / Q000502:physiology; D006352:Heart Ventricles / Q000196:embryology* / Q000378:metabolism; D000072576:Homeobox Protein Nkx-2.5; D053779:Latent TGF-beta Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008648:Mesoderm / Q000196:embryology* / Q000378:metabolism / Q000502:physiology; D009928:Organ Specificity / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D053779:Latent TGF-beta Binding Proteins; C580770:Ltbp3 protein, zebrafish; C528182:Nkx2.5 protein, zebrafish; D014157:Transcription Factors; D029961:Zebrafish Proteins