The Wilms’ tumour suppressor Wt1 is a major regulator of tumour angiogenesis and progression

Wagner, Kay-Dietrich; Cherfils‐Vicini, Julien; Hosen, Naoki; Hohenstein, Peter; Gilson, Éric; Hastie, Nicholas D.; Michiels, Jean‐François; Wagner, Nicole

doi:10.1038/ncomms6852

Cited by 84 publications

(94 citation statements)

References 65 publications

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“…The angiogenic role of WT1 is supported by a reduced sprouting capacity in an aortic ring angiogenesis assay from mice lacking WT1 expression in endothelial cells. In addition, the same study revealed that the vessel density in matrigel plugs after subcutaneously injection, in mice lacking WT1 expression in endothelial cells, is significantly reduced compared to wild-type animals (71). Furthermore, deletion of WT1 in endothelial cells resulted in major reduction in cardiac vessel formation during mouse cardiac development supporting the presence of WT1 and the essential role of WT in cardiac endothelial cells (86).…”

Section: The Role Of Wt1 In Endothelial Cellsmentioning

confidence: 67%

“…Although the expression of WT1 in cardiac endothelial cells is unique during normal conditions, the expression is also present in endothelial cells in other organs in a pathological condition. WT1 is found in endothelial cells of the skin in patients with chronic dermatitis (69), and WT1 has been observed in endothelial cells in a wide variety of tumors (68)(69)(70)(71)(72).…”

Section: The Role Of Wt1 In Endothelial Cellsmentioning

confidence: 99%

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WT1 in Cardiac Development and Disease

2016

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The heart is essential for realizing the distribution of oxygen and nutrients throughout the body. Therefore, the heart is the first organ to develop and is already functional in its most primitive structure during embryogenesis. Recent studies indicate that the transcription factor Wilms' tumor-1 (WT1) is important for many aspects of cardiac development. WT1 expression is first observed in the proepicardium, a group of progenitor cells that give rise to a mesothelial sheet covering the heart, the epicardium. WT1 expression in epicardial cells is required for their epithelial-to-mesenchymal transformation forming epicardium-derived cells that will contribute to the formation of coronary vessels and interstitial fibroblasts. Endothelial cells within the heart also express WT1, whereas the endothelial cells in other Duim et al. 212 parts of the embryo do not. The endothelial expression of WT1 during cardiac development is likely to be important for vascular formation. After cardiac injury, WT1 is temporally upregulated in the epicardium and in the endothelial cells in the infarcted area and border zone, which points to a potential important role for WT1 in cardiac repair and regeneration. In this chapter, we describe the many faces of WT1 within the heart.

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Section: The Role Of Wt1 In Endothelial Cellsmentioning

confidence: 67%

Section: The Role Of Wt1 In Endothelial Cellsmentioning

confidence: 99%

WT1 in Cardiac Development and Disease

2016

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“…Furthermore, a Wt1-GFP transgene is expressed in a population of visceral CD34 + Sca1 + stromal vascular fraction that are enriched for adipogenic progenitors suggesting Wt1 might also function in visceral adipocyte development [79]. Wt1 precursors are multipotent, generating testicles, ovaries, kidneys, spleen, adrenal glands, the mesothelial layer of visceral organs, and endothelial cells [79, 80]. Thus, a lineage marker that specifically labels all visceral white adipocytes has not been identified.…”

Section: Tissue Resident Adipocyte Progenitorsmentioning

confidence: 99%

Emerging Complexities in Adipocyte Origins and Identity

Sánchez-Gurmaches

Hung

Guertin

2016

Trends in Cell Biology

191

152

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The global incidence of obesity and its comorbidities continues to rise along with a demand for novel therapeutic interventions. Brown adipose tissue (BAT) is attracting attention as a therapeutic target because of its presence in adult humans and high capacity to dissipate energy as heat, and thus burn excess calories, when stimulated. Another potential avenue for therapeutic intervention is to induce, within white adipose tissue (WAT), the formation of brown-like adipocytes called brite (brown-like-in-white) or beige adipocytes. However, understanding how to harness the potential of these thermogenic cells requires a deep understanding of their developmental origins and regulation. Recent cell labeling and lineage tracing experiments are beginning to shed light on this emerging area of adipocyte biology. Here, we review adipocyte development giving particular attention to thermogenic adipocytes.

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“…To prove that coronary vascular defects in G2-Gata4 Cre ;Wt1 LoxP/LoxP mutants are not caused by disrupted epicardial signaling, we crossed Tie2 CreERT2 (18) and Wt1 LoxP/LoxP mice to create endothelial cell-specific Wt1 knockouts (19). Tamoxifen was injected at E10; the specificity of tamoxifen-induced recombination is shown in Fig.…”

Section: G2-gata4mentioning

confidence: 99%

Extracardiac septum transversum/proepicardial endothelial cells pattern embryonic coronary arterio–venous connections

Cano

Carmona

Ruiz‐Villalba

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

114

122

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Recent reports suggest that mammalian embryonic coronary endothelium (CoE) originates from the sinus venosus and ventricular endocardium. However, the contribution of extracardiac cells to CoE is thought to be minor and nonsignificant for coronary formation. Using classic (Wt1 Cre ) and previously undescribed (G2-Gata4 Cre ) transgenic mouse models for the study of coronary vascular development, we show that extracardiac septum transversum/ proepicardium (ST/PE)-derived endothelial cells are required for the formation of ventricular coronary arterio-venous vascular connections. Our results indicate that at least 20% of embryonic coronary arterial and capillary endothelial cells derive from the ST/PE compartment. Moreover, we show that conditional deletion of the ST/PE lineage-specific Wilms' tumor suppressor gene (Wt1) in the ST/PE ofG2-Gata4 Cre mice and in the endothelium of Tie2 Cre mice disrupts embryonic coronary transmural patterning, leading to embryonic death. Taken together, our results demonstrate that ST/PE-derived endothelial cells contribute significantly to and are required for proper coronary vascular morphogenesis.T he coronary vascular system, whose function is necessary to sustain late embryonic and postnatal cardiac function, is formed by a complex network of blood vessels, including arteries, arterioles, capillaries, venules, and veins (1). Recent reports indicate that various sources of endothelial cells contribute to the mammalian embryonic coronary system (2-4). However, the specific fate and function of these different endothelial cell pools during coronary vascular morphogenesis is the subject of intense controversy (5).Two endocardial populations have been reported to participate in the building of the embryonic coronary vascular system. The first derives from the sinus venosus endocardium, which sprouts to give rise to the nascent Apelin + coronary vasculature (2). A careful analysis of this study suggests that the sinus venosus endocardium, which is able to vascularize subepicardial and myocardial heart layers, mainly provides a cellular scaffold for the development of coronary veins (CoV). Accordingly, a second source of coronary endothelium (CoE) has been identified in the ventricular endocardium (Nfatc1 + lineage), which contributes massively to coronary arterial (CoA) endothelium (3, 6).A third disputed source of CoE is the proepicardium (PE), a structure that comprises epicardial progenitor cells. The PE protrudes from the septum transversum (ST), a folding of the lateral mesoderm that initiates the separation of thoracic and abdominal cavities in mammals (7). Although in vivo cell tracing and in vitro culture of avian PE cells clearly shows that PE cells can differentiate into CoE (8, 9), data from studies in mammals claimed the contribution of PE to CoE is minor (10-12). The so-called "epicardial" Cre constructs used in these studies are based on the expression of genes such as Gata5, Tbx18, or Wilms' tumor suppressor (Wt1) ( Table S1), all of which are expressed by both PE and...

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The Wilms’ tumour suppressor Wt1 is a major regulator of tumour angiogenesis and progression

Cited by 84 publications

References 65 publications

WT1 in Cardiac Development and Disease

WT1 in Cardiac Development and Disease

Emerging Complexities in Adipocyte Origins and Identity

Extracardiac septum transversum/proepicardial endothelial cells pattern embryonic coronary arterio–venous connections

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