Second heart field cardiac progenitor cells in the early mouse embryo

Francou, Alexandre; Saint-Michel, Edouard; Mesbah, Karim; Théveniau-Ruissy, Magali; Rana, M. Sameer; Christoffels, Vincent M.; Kelly, Robert G.

doi:10.1016/j.bbamcr.2012.10.003

Cited by 45 publications

(36 citation statements)

References 48 publications

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“…The SHF gives rise to two spatially different populations: the anterior SHF, which is adjacent to the arterial pole, and the posterior SHF, which is adjacent to the venous pole (108). The posterior SHF contributes to the DMP, an essential structure for chamber septation (109).…”

Section: Nfp Regulates Atrioventricular Septation Via Dmp Formationmentioning

confidence: 99%

Numb family proteins: novel players in cardiac morphogenesis and cardiac progenitor cell differentiation

2015

Biomolecular Concepts

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Vertebrate heart formation is a spatiotemporally regulated morphogenic process that initiates with bilaterally symmetric cardiac primordial cells migrating toward the midline to form a linear heart tube. The heart tube then elongates and undergoes a series of looping morphogenesis, followed by expansions of regions that are destined to become primitive heart chambers. During the cardiac morphogenesis, cells derived from the first heart field contribute to the primary heart tube, and cells from the secondary heart field, cardiac neural crest, and pro-epicardial organ are added to the heart tube in a precise spatiotemporal manner. The coordinated addition of these cells and the accompanying endocardial cushion morphogenesis yield the atrial, ventricular, and valvular septa, resulting in the formation of a 4-chambered heart. Perturbation of progenitor cells’ deployment and differentiation leads to a spectrum of congenital heart diseases. Two of the genes that were recently discovered to be involved in cardiac morphogenesis are Numb and Numblike. Numb, an intracellular adaptor protein, distinguishes sibling cell fates by its asymmetric distribution between the two daughter cells and its ability to inhibit Notch signaling. Numb regulates cardiac progenitor cell differentiation in Drosophila, and controls heart tube laterality in Zebrafish. In mice, Numb and Numblike, the Numb Family Proteins (NFPs), function redundantly and have been shown to be essential for epicardial development, cardiac progenitor cell differentiation, outflow tract alignment, atrioventricular septum morphogenesis, myocardial trabeculation and compaction. In this review, we will summarize the functions of NFPs in cardiac development, and discuss potential mechanisms of NFPs in the regulation of cardiac development.

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Section: Nfp Regulates Atrioventricular Septation Via Dmp Formationmentioning

confidence: 99%

Numb family proteins: novel players in cardiac morphogenesis and cardiac progenitor cell differentiation

2015

Biomolecular Concepts

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“…Understanding the mechanisms behind myocardial growth and maturation will aid the detection of NCM and amelioration of its consequences. While the intercellular signals that guide the specification, maintenance, and differentiation of cardiac progenitor cells have been described (Francou et al, 2013; Rochais et al, 2009; Tzahor, 2007; Zaffran and Kelly, 2012), those guiding their cytoskeletal rearrangements and morphogenesis into adult myocardium remain unclear.…”

Section: Introductionmentioning

confidence: 99%

DAAM1 and DAAM2 are co-required for myocardial maturation and sarcomere assembly

Ajima

Bisson

Helt

et al. 2015

Developmental Biology

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Wnt ligands regulate heart morphogenesis but the underlying mechanisms remain unclear. Two Formin-related proteins, DAAM1 and 2, were previously found to bind the Wnt effector Disheveled. Here, since DAAM1 and 2 nucleate actin and mediate Wnt-induced cytoskeletal changes, a floxed-allele of Daam1 was used to disrupt its function specifically in the myocardium and investigate Wnt-associated pathways. Homozygous Daam1 conditional knockout (CKO) mice were viable but had misshapen hearts and poor cardiac function. The defects in Daam1 CKO mice were observed by mid-gestation and were associated with a loss of protrusions from cardiomyocytes invading the outflow tract. Further, these mice exhibited noncompaction cardiomyopathy (NCM) and deranged cardiomyocyte polarity. Interestingly, Daam1 CKO mice that were also homozygous for an insertion disrupting Daam2 (DKO) had stronger NCM, severely reduced cardiac function, disrupted sarcomere structure, and increased myocardial proliferation, suggesting that DAAM1 and DAAM2 have redundant functions. While RhoA was unaffected in the hearts of Daam1/2 DKO mice, AKT activity was lower than in controls, raising the issue of whether DAAM1/2 are only mediating Wnt signaling. Daam1-floxed mice were thus bred to Wnt5a null mice to identify genetic interactions. The hearts of Daam1 CKO mice that were also heterozygous for the null allele of Wnt5a had stronger NCM and more severe loss of cardiac function than Daam1 CKO mice, consistent with DAAM1 and Wnt5a acting in a common pathway. However, deleting Daam1 further disrupted Wnt5a homozygousnull hearts, suggesting that DAAM1 also has Wnt5a-independent roles in cardiac development.

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“…Nonetheless, recent studies point to continued DNA synthesis and therefore to neomyocardialization potential in adult hearts [17], [18]. On the other hand cardiomyocyte differentiation occurs early in heart morphogenesis and persists until the first weeks of birth [19]. Thus the balance between cellular proliferation and differentiation during heart formation is crucial to provide the progressive thickening and maturation of the cardiac myoarchitecture [20].…”

Section: Introductionmentioning

confidence: 99%

Targeted Inactivation of Cerberus Like-2 Leads to Left Ventricular Cardiac Hyperplasia and Systolic Dysfunction in the Mouse

2014

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Previous analysis of the Cerberus like 2 knockout (Cerl2−/−) mouse revealed a significant mortality during the first day after birth, mostly due to cardiac defects apparently associated with randomization of the left-right axis. We have however, identified Cerl2-associated cardiac defects, particularly a large increase in the left ventricular myocardial wall in neonates that cannot be explained by laterality abnormalities. Therefore, in order to access the endogenous role of Cerl2 in cardiogenesis, we analyzed the embryonic and neonatal hearts of Cerl2 null mutants that did not display a laterality phenotype. Neonatal mutants obtained from the compound mouse line Cer2−/−::Mlc1v-nLacZ24+, in which the pulmonary ventricle is genetically marked, revealed a massive enlargement of the ventricular myocardium in animals without laterality defects. Echocardiography analysis in Cerl2−/− neonates showed a left ventricular systolic dysfunction that is incompatible with a long lifespan. We uncovered that the increased ventricular muscle observed in Cerl2−/− mice is caused by a high cardiomyocyte mitotic index in the compact myocardium which is mainly associated with increased Ccnd1 expression levels in the left ventricle at embryonic day (E) 13. Interestingly, at this stage we found augmented left ventricular expression of Cerl2 levels when compared with the right ventricle, which may elucidate the regionalized contribution of Cerl2 to the left ventricular muscle formation. Importantly, we observed an increase of phosphorylated Smad2 (pSmad2) levels in embryonic (E13) and neonatal hearts indicating a prolonged TGFβs/Nodal-signaling activation. Concomitantly, we detected an increase of Baf60c levels, but only in Cerl2−/− embryonic hearts. These results indicate that independently of its well-known role in left-right axis establishment Cerl2 plays an important role during heart development in the mouse, mediating Baf60c levels by exerting an important control of the TGFβs/Nodal-signaling pathway.

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Second heart field cardiac progenitor cells in the early mouse embryo

Cited by 45 publications

References 48 publications

Numb family proteins: novel players in cardiac morphogenesis and cardiac progenitor cell differentiation

Numb family proteins: novel players in cardiac morphogenesis and cardiac progenitor cell differentiation

DAAM1 and DAAM2 are co-required for myocardial maturation and sarcomere assembly

Targeted Inactivation of Cerberus Like-2 Leads to Left Ventricular Cardiac Hyperplasia and Systolic Dysfunction in the Mouse

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