Canonical WNT Signaling Enhances Stem Cell Expression in the Developing Heart Without a Corresponding Inhibition of Cardiogenic Differentiation

Martin, L.; Mezentseva, Nadejda V.; Bratoeva, Momka; Ramsdell, Ann F.; Eisenberg, Carol A.; Eisenberg, Leonard M.

doi:10.1089/scd.2010.0490

Cited by 11 publications

(20 citation statements)

References 72 publications

(115 reference statements)

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“…Thus, the data demonstrate that‐exposure of the whole embryo to lithium at the onset of gastrulation (i.e., stage 10) inhibited formation of the heart and differentiation of precardiac mesoderm to myocytes. In contrast, treatment of embryos at stage 10 with high doses of the GSK3 inhibitor SB415286 (Martin et al. 2011) did not hinder development of contractile hearts (Fig.…”

Section: Resultsmentioning

confidence: 93%

“…(G) Summary of experiments where Xenopus embryos were exposed to 300 mmol/L lithium for 10 min at either stages 9, 10, 11, or 12 ( n = 9, 21, 9, 6, respectively). In parallel dishes, embryos were treated at stage 10 with 4 mmol/L SB415286 for 10 min ( n = 19), which is the optimized dose of this selective GSK3 inhibitor (Martin et al. 2011).…”

Section: Resultsmentioning

confidence: 99%

“…2000; Schneider & Mercola 2001). Comparative qPCR analysis was performed with the StepOne plus qPCR system (Applied BioSystems) using TaqMan qPCR Master Mix (Applied BioSystems), as described (Martin et al. 2011).…”

Section: Methodsmentioning

confidence: 99%

“…2011). Primer pairs and probes used for qPCR (Martin et al. 2011) were specific for elongation factor 1α (EF1α), GATA6, Tbx5, Tbx20, Nkx2.5, cardiac α actin (Actc), cardiac myosin heavy chain‐α (cMHCα), and cardiac troponin I (cTnI).…”

Section: Methodsmentioning

confidence: 99%

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Inhibition of heart formation by lithium is an indirect result of the disruption of tissue organization within the embryo

et al. 2011

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Lithium is a commonly used drug for the treatment of bipolar disorder. At high doses, lithium becomes teratogenic, which is a property that has allowed this agent to serve as a useful tool for dissecting molecular pathways that regulate embryogenesis. This study was designed to examine the impact of lithium on heart formation in the developing frog for insights into the molecular regulation of cardiac specification. Embryos were exposed to lithium at the beginning of gastrulation, which produced severe malformations of the anterior end of the embryo. Although previous reports characterized this deformity as a posteriorized phenotype, histological analysis revealed that the defects were more comprehensive, with disfigurement and disorganization of all interior tissues along the anterior-posterior axis. Emerging tissues were poorly segregated and cavity formation was decreased within the embryo. Lithium exposure also completely ablated formation of the heart and prevented myocardial cell differentiation. Despite the complete absence of cardiac tissue in lithium treated embryos, exposure to lithium did not prevent myocardial differentiation of precardiac DMZ explants. Moreover, precardiac tissue freed from the embryo subsequent to lithium treatment at gastrulation gave rise to cardiac tissue, as demonstrated by upregulation of cardiac gene expression, display of sarcomeric proteins, and formation of a contractile phenotype. Together these data indicate that lithium’s effect on the developing heart was not due to direct regulation of cardiac differentiation, but an indirect consequence of disrupted tissue organization within the embryo.

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Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Inhibition of heart formation by lithium is an indirect result of the disruption of tissue organization within the embryo

et al. 2011

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“…Using tissue explant to study cardiogenesis has been performed on both Xenopus and chicken [44–47]. We also included markers of lymphatic development and mesonephros formation (summarized in electronic supplementary material, table S2).…”

Section: Resultsmentioning

confidence: 99%

Nodal signalling inXenopus: the role of Xnr5 in left/right asymmetry and heart development

et al. 2016

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Nodal class TGF-β signalling molecules play essential roles in establishing the vertebrate body plan. In all vertebrates, nodal family members have specific waves of expression required for tissue specification and axis formation. In Xenopus laevis, six nodal genes are expressed before gastrulation, raising the question of whether they have specific roles or act redundantly with each other. Here, we examine the role of Xnr5. We find it acts at the late blastula stage as a mesoderm inducer and repressor of ectodermal gene expression, a role it shares with Vg1. However, unlike Vg1, Xnr5 depletion reduces the expression of the nodal family member xnr1 at the gastrula stage. It is also required for left/right laterality by controlling the expression of the laterality genes xnr1, antivin (lefty) and pitx2 at the tailbud stage. In Xnr5-depleted embryos, the heart field is established normally, but symmetrical reduction in Xnr5 levels causes a severely stunted midline heart, first evidenced by a reduction in cardiac troponin mRNA levels, while left-sided reduction leads to randomization of the left/right axis. This work identifies Xnr5 as the earliest step in the signalling pathway establishing normal heart laterality in Xenopus.

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Cardiac Stem Cells and their Roles in Myocardial Infarction

Hou

Wang

Jiang

et al. 2012

Stem Cell Rev and Rep

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Myocardial infarction leads to loss of cardiomyocytes, scar formation, ventricular remodeling and eventually deterioration of heart function. Over the past decade, stem cell therapy has emerged as a novel strategy for patients with ischemic heart disease and its beneficial effects have been demonstrated by substantial preclinical and clinical studies. Efficacy of several types of stem cells in the therapy of cardiovascular diseases has already been evaluated. However, repair of injured myocardium through stem cell transplantation is restricted by critical safety issues and ethic concerns. Recently, the discovery of cardiac stem cells (CSCs) that reside in the heart itself brings new prospects for myocardial regeneration and reconstitution of cardiac tissues. CSCs are positive for various stem cell markers and have the potential of self-renewal and multilineage differentiation. They play a pivotal role in the maintenance of heart homeostasis and cardiac repair. Elucidation of their biological characteristics and functions they exert in myocardial infarction are very crucial to further investigations on them. This review will focus on the field of cardiac stem cells and discuss technical and practical issues that may involve in their clinical applications in myocardial infarction.

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Canonical WNT Signaling Enhances Stem Cell Expression in the Developing Heart Without a Corresponding Inhibition of Cardiogenic Differentiation

Cited by 11 publications

References 72 publications

Inhibition of heart formation by lithium is an indirect result of the disruption of tissue organization within the embryo

Inhibition of heart formation by lithium is an indirect result of the disruption of tissue organization within the embryo

Nodal signalling inXenopus: the role of Xnr5 in left/right asymmetry and heart development

Cardiac Stem Cells and their Roles in Myocardial Infarction

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