Comprehensive Gene-Expression Survey Identifies Wif1 as a Modulator of Cardiomyocyte Differentiation

Buermans, Henk P.J.; Wijk, Bram van; Hulsker, Margriet; Smit, Niels C. H.; Dunnen, Johan T. den; Ommen, Gert‐Jan B. van; Moorman, Antoon F.M.; Hoff, Maurice J.B. van den; Hoen, Peter A C ‘t

doi:10.1371/journal.pone.0015504

Cited by 17 publications

(21 citation statements)

References 53 publications

(68 reference statements)

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“…4, A-F). Recombinant human WIF1 protein is 93% homologous to the mouse ortholog, and its ability to impair WNT/␤-catenin signaling was demonstrated previously in an array of species and tissues including Xenopus embryo, chicken heart, and mouse thymus (35)(36)(37). Whole-mount ISH was performed as described previously to visualize and quantify the Nkx3-1-positive prostatic buds formed per the UGS (24).…”

Section: Androgens Are Necessary and Sufficient Formentioning

confidence: 83%

“…6), we cannot exclude the possibility that it causes small changes that we were unable to detect. We do not fully understand the concentration-response relationship between ␤-catenin activity and prostatic bud formation and minor changes in this signaling pathway could account for biologically sig- (36). Therefore, although WNT/␤-catenin-responsive Axin2 and Lef1 mRNA patterns were not noticeably changed in UGS explants exposed to WIF1, it is possible that we failed to detect subtle or finely localized WIF1-mediated changes in WNT signaling that were important in shaping the pattern and number of prostatic buds formed in the developing mouse UGS.…”

Section: Possible Mechanisms By Which Wif1 Could Enhance Fetal Prostamentioning

confidence: 99%

“…The most widely accepted Wif1 mechanism of action is functional antagonism of WNT/␤-catenin signaling (35,36,38). Yet in developing mouse prostate, Wif1 is expressed in UGM and UGE and overlaps WNT/␤-cateninresponsive Axin2 and Lef1 (lymphoid enhancer binding factor 1) expression (14,15,19).…”

Section: Exogenous Wif1 Does Not Change the Pattern Of Wnt/␤-catenin mentioning

confidence: 99%

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Wnt Inhibitory Factor 1 (Wif1) Is Regulated by Androgens and Enhances Androgen-Dependent Prostate Development

et al. 2012

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Fetal prostate development from urogenital sinus (UGS) epithelium requires androgen receptor (AR) activation in UGS mesenchyme (UGM). Despite growing awareness of sexually dimorphic gene expression in the UGS, we are still limited in our knowledge of androgen-responsive genes in UGM that initiate prostate ductal development. We found that WNT inhibitory factor 1 (Wif1) mRNA is more abundant in male vs. female mouse UGM in which its expression temporally and spatially overlaps androgen-responsive steroid 5␣-reductase 2 (Srd5a2). Wif1 mRNA is also present in prostatic buds during their elongation and branching morphogenesis. Androgens are necessary and sufficient for Wif1 expression in mouse UGS explant mesenchyme, and testicular androgens remain necessary for normal Wif1 expression in adult mouse prostate stroma. WIF1 contributes functionally to prostatic bud formation. In the presence of androgens, exogenous WIF1 protein increases prostatic bud number and UGS basal epithelial cell proliferation without noticeably altering the pattern of WNT/␤-catenin-responsive Axin2 or lymphoid enhancer binding factor 1 (Lef1) mRNA. Wif1 mutant male UGSs exhibit increased (Sfrp)2 and (Sfrp)3 expression and form the same number of prostatic buds as the wild-type control males. Collectively our results reveal Wif1 as one of the few known androgen-responsive genes in the fetal mouse UGM and support the hypothesis that androgen-dependent Wif1 expression is linked to the mechanism of androgen-induced prostatic bud formation. (Endocrinology 153: 6091-6103, 2012) A ndrogens initiate prostatic bud formation from the urogenital sinus (UGS) and stimulate prostatic bud elongation, ductal branching morphogenesis, and differentiation of mature prostatic ductal epithelium (1, 2). During fetal prostate development, androgens activate androgen receptors (ARs) in UGS mesenchyme (UGM) to induce prostatic bud formation in UGS epithelium (UGE) (1, 3-5). The developing prostate has therefore been used as a model to assess the role of androgens in mesenchymal/epithelial interactions. A longstanding question in the prostate development field is how ARs in UGM communicate with UGE to establish the pattern and quantity of prostatic buds that will form. Continued investigation is expected to shed light on how the developing prostate microenvironment influences prostate epithelial cell fate. It may also elucidate how adult prostate stromal ARs reactivate developmental signaling pathways to cause inappropriate proliferative growth during prostate disease (6 -13).Numerous gene expression profiling studies have been conducted to identify androgen-responsive mRNAs in fe-

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Section: Androgens Are Necessary and Sufficient Formentioning

confidence: 83%

Section: Possible Mechanisms By Which Wif1 Could Enhance Fetal Prostamentioning

confidence: 99%

Section: Exogenous Wif1 Does Not Change the Pattern Of Wnt/␤-catenin mentioning

confidence: 99%

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Wnt Inhibitory Factor 1 (Wif1) Is Regulated by Androgens and Enhances Androgen-Dependent Prostate Development

et al. 2012

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“…EPDCs proliferate and differentiate into several different cell types, including coronary endothelial cells, smooth muscle cells, and fibroblasts (Mikawa and Gourdie, ; Landerholm et al, ; Guadix et al, ; Pennisi and Mikawa, ; Zhou et al, ; Kikuchi et al, ; Acharya et al, ; Katz et al, ; Cano et al, ), but not lymphatic endothelial cells, as has been shown by Wilting et al (). There are disputable data claiming that EPDCs may also differentiate into cardiomyocytes, but these results need to be further confirmed (Cai et al, ; Zhou et al, ; Christoffels et al, ; Buermans et al, ). The results obtained with lineage‐tracing experiments are also inconclusive because the markers expressed in the PE, epicardium, and EPDCs change dynamically and can be expressed in various sites of a developing heart.…”

Section: Introductionmentioning

confidence: 98%

Proepicardium: Current Understanding of its Structure, Induction, and Fate

Niderla-Bielińska

Jankowska‐Steifer

Flaht-Zabost

et al. 2018

The Anatomical Record

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The proepicardium (PE) is a transitory extracardiac embryonic structure which plays a crucial role in cardiac morphogenesis and delivers various cell lineages to the developing heart. The PE arises from the lateral plate mesoderm (LPM) and is present in all vertebrate species. During development, mesothelial cells of the PE reach the naked myocardium either as free‐floating aggregates in the form of vesicles or via a tissue bridge; subsequently, they attach to the myocardium and, finally, form the third layer of a mature heart—the epicardium. After undergoing epithelial‐to‐mesenchymal transition (EMT) some of the epicardial cells migrate into the myocardial wall and differentiate into fibroblasts, smooth muscle cells, and possibly other cell types. Despite many recent findings, the molecular pathways that control not only proepicardial induction and differentiation but also epicardial formation and epicardial cell fate are poorly understood. Knowledge about these events is essential because molecular mechanisms that occur during embryonic development have been shown to be reactivated in pathological conditions, for example, after myocardial infarction, during hypertensive heart disease or other cardiovascular diseases. Therefore, in this review we intended to summarize the current knowledge about PE formation and structure, as well as proepicardial cell fate in animals commonly used as models for studies on heart development. Anat Rec, 302:893–903, 2019. © 2018 Wiley Periodicals, Inc.

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“…The role of Wnt signals in the context of proepicardium formation has thus far only been poorly studied. Several Wnt pathway genes are expressed in the proepicardium including Wnt2a and Wnt5b, the Frizzled receptors Fzd1, Fzd7, Frzb, Dkk1, Dkk2 and Wif1 [88]. There is evidence that Wif1 appears to be involved in allocating lateral plate mesoderm precursor cells to enter either the PE or myocardial lineage [88].…”

Section: Wnt Signals In Pe Formationmentioning

confidence: 99%

Origin and fates of the proepicardium

Schlueter

Brand

2011

Aswan Heart Centre Science &Amp; Practice Series

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The embryonic heart initially consists of only two cell layers, the endocardium and the myocardium. The epicardium, which forms an epithelial layer on the surface of the heart, is derived from a cluster of mesothelial cells developing at the base of the venous inflow tract of the early embryonic heart. This cell cluster is termed the proepicardium and gives rise not only to the epicardium but also to epicardium-derived cells. These cells populate the myocardial wall and differentiate into smooth muscle cells and fibroblasts, while the contribution to the vascular endothelial lineage is uncertain. In this review we will discuss the signaling molecules involved in recruiting mesodermal cells to undergo proepicardium formation and guide these cells to the myocardial surface. Marker genes which are suitable to follow these cells during proepicardium formation and cell migration will be introduced. We will address whether the proepicardium consists of a homogenous cell population or whether different cell lineages are present. Finally the role of the epicardium as a source for cardiac stem cells and its importance in cardiac regeneration, in particular in the zebrafish and mouse model systems is discussed

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Comprehensive Gene-Expression Survey Identifies Wif1 as a Modulator of Cardiomyocyte Differentiation

Cited by 17 publications

References 53 publications

Wnt Inhibitory Factor 1 (Wif1) Is Regulated by Androgens and Enhances Androgen-Dependent Prostate Development

Wnt Inhibitory Factor 1 (Wif1) Is Regulated by Androgens and Enhances Androgen-Dependent Prostate Development

Proepicardium: Current Understanding of its Structure, Induction, and Fate

Origin and fates of the proepicardium

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