Zebrafish second heart field development relies on progenitor specification in anterior lateral plate mesoderm and <i>nkx2.5</i> function

Guner-Ataman, Burcu; Paffett-Lugassy, Noëlle; Adams, Meghan S.; Nevis, Kathleen R.; Jahangiri, Leila; Obregón, Pablo Orozco; Kikuchi, Kazu; Poss, Kenneth D.; Burns, Caroline E.; Burns, C. Geoffrey

doi:10.1242/dev.088351

Cited by 93 publications

(92 citation statements)

References 62 publications

(131 reference statements)

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“…However, downregulated expression of ltbp3, an SHF marker (Zhou et al, 2011), in nkx2.5 mutant embryos (supplementary material Fig. S8A,C) suggests that there could be diminished contribution from the SHF, consistent with a recent report demonstrating reduced ltbp3 expression and reduced production of SHF-derived cardiomyocytes in embryos injected with an anti-nkx2.5 MO (Guner-Ataman et al, 2013 Fig. S8E), further highlighting the impact of Nkx gene function on regulation of ltbp3.…”

Section: Transformation From Ventricular To Atrial Identity In the Absupporting

confidence: 86%

Nkx genes are essential for maintenance of ventricular identity

et al. 2013

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SUMMARYEstablishment of specific characteristics of each embryonic cardiac chamber is crucial for development of a fully functional adult heart. Despite the importance of defining and maintaining unique features in ventricular and atrial cardiomyocytes, the regulatory mechanisms guiding these processes are poorly understood. Here, we show that the homeodomain transcription factors Nkx2.5 and Nkx2.7 are necessary to sustain ventricular chamber attributes through repression of atrial chamber identity. Mutation of nkx2.5 in zebrafish yields embryos with diminutive ventricular and bulbous atrial chambers. These chamber deformities emerge gradually during development, with a severe collapse in the number of ventricular cardiomyocytes and an accumulation of excess atrial cardiomyocytes as the heart matures. Removal of nkx2.7 function from nkx2.5 mutants exacerbates the loss of ventricular cells and the gain of atrial cells. Moreover, in these Nkx-deficient embryos, expression of vmhc, a ventricular gene, fades, whereas expression of amhc, an atrial gene, expands. Cell-labeling experiments suggest that ventricular cardiomyocytes can transform into atrial cardiomyocytes in the absence of Nkx gene function. Through suggestion of transdifferentiation from ventricular to atrial fate, our data reveal a pivotal role for Nkx genes in maintaining ventricular identity and highlight remarkable plasticity in differentiated myocardium. Thus, our results are relevant to the etiologies of fetal and neonatal cardiac pathology and could direct future innovations in cardiac regenerative medicine.

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Section: Transformation From Ventricular To Atrial Identity In the Absupporting

confidence: 86%

Nkx genes are essential for maintenance of ventricular identity

et al. 2013

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“…It was shown that, as in higher vertebrates, this region contributes to endocardial cells but only within the outflow tract region of the heart; no contribution to endocardial cells within the main chambers was detected. It was further shown, using Cre/loxP-mediated lineage tracing of GATA binding protein 4 + (gata4 + ) and nkx2.5 + cell populations, that zebrafish secondary heart field progenitors are specified within the ALPM and contribute to endocardial cells only within the outflow tract region of the heart (Guner- Ataman et al, 2013). In line with this, and in contrast to higher vertebrates in which secondary heart field-derived endocardial cells contribute to a large portion of the right ventricular endocardium (Cai et al, 2003;Milgrom-Hoffman et al, 2011;Moretti et al, 2006;Verzi et al, 2005), endocardial growth of the zebrafish main cardiac chambers is largely independent of a secondary heart field contribution (Lazic and Scott, 2011;Dietrich et al, 2014).…”

Section: Developmental Origins Of the Endocardiummentioning

confidence: 99%

The force within: endocardial development, mechanotransduction and signalling during cardiac morphogenesis

Haack

Abdelilah‐Seyfried

2016

Development

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Endocardial cells are cardiac endothelial cells that line the interior of the heart tube. Historically, their contribution to cardiac development has mainly been considered from a morphological perspective. However, recent studies have begun to define novel instructive roles of the endocardium, as a sensor and signal transducer of biophysical forces induced by blood flow, and as an angiocrine signalling centre that is involved in myocardial cellular morphogenesis, regeneration and reprogramming. In this Review, we discuss how the endocardium develops, how endocardial-myocardial interactions influence the developing embryonic heart, and how the dysregulation of blood flowresponsive endocardial signalling can result in pathophysiological changes.

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“…(1) EdU staining does not require DNA denaturation and therefore preserves the integrity of tissue; (2) EdU staining may conserve antigenicities for molecular markers; (3) EdU staining is much faster than BrdU staining (Guner-Ataman et al 2013). Our current findings show that EdU robustly labeled dividing cardiac cells in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 64%

Cardiac cell proliferation assessed by EdU, a novel analysis of cardiac regeneration

et al. 2014

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Emerging evidence suggests that mammalian hearts maintain the capacity for cardiac regeneration. Rapid and sensitive identification of cardiac cellular proliferation is prerequisite for understanding the underlying mechanisms and strategies of cardiac regeneration. The following immunologically related markers of cardiac cells were analyzed: cardiac transcription factors Nkx2.5 and Gata 4; specific marker of cardiomyocytes TnT; endothelial cell marker CD31; vascular smooth muscle marker smooth muscle myosin IgG; cardiac resident stem cells markers IsL1, Tbx18, and Wt1. Markers were colocalized in cardiac tissues of embryonic, neonatal, adult, and pathological samples by 5-ethynyl-2 0 -deoxyuridine (EdU) staining. EdU was also used to label isolated neonatal cardiomyocytes in vitro. EdU robustly labeled proliferating cells in vitro and in vivo, co-immunostaining with different cardiac cells markers. EdU can rapidly and sensitively label proliferating cardiac cells in developmental and pathological states. Cardiac cell proliferation assessed by EdU is a novel analytical tool for investigating the mechanism and strategies of cardiac regeneration in response to injury.

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Zebrafish second heart field development relies on progenitor specification in anterior lateral plate mesoderm and nkx2.5 function

Cited by 93 publications

References 62 publications

Nkx genes are essential for maintenance of ventricular identity

Nkx genes are essential for maintenance of ventricular identity

The force within: endocardial development, mechanotransduction and signalling during cardiac morphogenesis

Cardiac cell proliferation assessed by EdU, a novel analysis of cardiac regeneration

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