Wnt4 is essential to normal mammalian lung development

Caprioli, Arianna; Villasenor, Alethia; Wylie, Lyndsay A.; Braitsch, Caitlin M.; Marty-Santos, Leilani; Barry, David M.; Karner, Courtney M.; Fu, Stephen; Meadows, Stryder M.; Carroll, Thomas J.; Cleaver, Ondine

doi:10.1016/j.ydbio.2015.08.017

Cited by 55 publications

(45 citation statements)

References 55 publications

(61 reference statements)

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“…The Wnt signaling pathway is important for embryonic development, tissue regeneration and homeostasis (15,16). In the present study, certain Wnt signaling genes were observed to be aberrantly expressed in SCNT embryo, such as the expression of Wnt3A, FZ3, LEF1 and APC.…”

Section: Discussionmentioning

confidence: 50%

IWP2 impairs the development of porcine somatic cell nuclear transfer embryos via Wnt signaling pathway inactivation

Huang

Yuan

et al. 2017

Biomedical Reports

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Abstract. Wnt signaling is critical in embryonic development and post-embryonic tissue homeostasis. The aim of the present study was to evaluate the expression levels of canonical Wnt signaling genes in porcine somatic cell nuclear transfer (SCNT) embryos. Quantitative polymerase chain reaction analysis was performed in porcine SCNT embryos, and the results indicated that the temporal expression patterns of canonical signaling genes were similar between in vivo and SCNT embryos from the 2-cell to the blastocyst stage. In addition, aberrant expression in a small number of Wnt signaling genes in SCNT embryos was identified. IWP2, an inhibitor of Wnt processing, was applied to the culture of SCNT embryos. The Wnt signaling pathway in the SCNT blastocysts may be inactivated via IWP2 treatment, reflecting the low expression levels of c-Myc and peroxisome proliferator-activated receptor δ. Furthermore, blastocyst hatching was damaged by IWP2 treatment. These findings indicate that the canonical Wnt signaling pathway is important for SCNT embryo development. IntroductionSomatic cell nuclear transfer (SCNT) is an effective method of reprogramming differentiated nuclei and has many potential applications (1). Owing to incomplete or faulty reprogramming, however, the cloning efficiency of SCNT embryos remains low (2,3). Aberrant reprogramming leads to changes in the expression levels of certain genes important for embryonic development. Studies on the expression of development-associated genes may be valuable for improving the developmental competence of SCNT embryos.Wnt signaling is a critical regulator of many cellular and physiological processes. Wnt signaling regulates cell proliferation and differentiation, controls migration and patterning during embryonic development, and maintains tissue homeostasis in adults (4,5). Depending on the involvement of β-catenin, these signaling pathways have been classified as canonical (β-catenin-dependent) or non-canonical (β-catenin-independent) (6). In the canonical Wnt signaling pathway, which has been better examined (7), β-catenin accumulates in the cytoplasm and eventually translocates to the nucleus where it acts as a transcriptional co-activator of transcription factors belonging to the T-cell factor/lymphoid enhancer factor-1(TCF/LEF) family. β-catenin that accumulates in the cytoplasm is degraded, however, by a protein complex that includes axin, glycogen synthase kinase-3 (GSK-3), protein phosphatase 2A (PP2A), casein kinase 1 (CK1) and adenomatous polyposis coli (APC) (6,8). This degradation complex becomes disrupted as soon as the Wnt protein binds to receptors of frizzled (Fz) and low-density lipoprotein receptor-related protein (LRP5/6), which activates multiple signaling cascades.Dysfunctions in Wnt signaling result in severe complications of embryonic development. For example, abnormalities were observed in the size and shape of mouse embryos lacking intact maternal/zygotic β-catenin during pre-and post-implantation development (5). By contrast, transient expression...

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Section: Discussionmentioning

confidence: 50%

IWP2 impairs the development of porcine somatic cell nuclear transfer embryos via Wnt signaling pathway inactivation

Huang

Yuan

et al. 2017

Biomedical Reports

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“…Following Tbx4 expression, Gli1 (a direct S onic H edge h og (Shh) signaling transcriptional target) is detected at E10.5–11.5[9], and it remains activated for the development of bronchial and vascular smooth muscle cells and various stromal cell populations in murine lungs[9, 10]. Following Shh signaling, it is speculated that Wnt singling is required for further differentiation of mesodermal progenitors into pericytes, resident interstitial fibroblasts, and smooth muscle cells[9, 11, 12]. Pericytes appear to arise from Foxn1 -expressing perivascular progenitor cells, which were shown to give rise to several distinct populations of PDGFRß + NG2 + pericytes, some of which co-express PDGFRα and collagen 1[13].…”

Section: Mesodermal Development In the Lungmentioning

confidence: 99%

Heterogeneity of Fibroblasts and Myofibroblasts in Pulmonary Fibrosis

Habiel

Hogaboam

2017

Curr Pathobiol Rep

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Purpose of review Idiopathic Pulmonary Fibrosis (IPF) is the most common form of interstitial lung diseases of unknown eathiopathogenesis, mean survival of 3-5 years and limited therapeutics. Characterized by a loss of alveolar type II epithelial cells and aberrant activation of stromal cells, considerable effort was undertaken to characterize the origin and activation mechanisms of fibroblasts and myofibroblasts in IPF lungs. In this review, the origin and contribution of fibroblast and myofibroblasts in lung fibrosis will be summarized. Recent findings Lineage tracing experiments suggested that interstitial lung fibroblasts and lipofibroblasts, pericytes and mesothelial cells differentiate into myofibroblasts. However, epithelial and bone marrow derived cells may give rise to collagen expressing fibroblasts but do not differentiate into myofibroblasts. Summary There is great heterogeneity in fibroblasts and myofibroblasts in fibrotic lungs. Further, there is evidence for the expansion of pericyte derived myofibroblasts and loss of lipofibroblasts and lipofibroblast derived myofibroblasts in IPF.

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“…We examined tumors related to tissues that require WNT4 in development (eg. kidney, adrenal, lung, ovary, uterus [45][46][47][48]), and identified tumors that over-expressed WNT4 mRNA (Figure 5A). Comparing WNT4 high versus other tumors, we looked for differences in protein signaling in RPPA data (reverse phase protein array).…”

Section: Atypical Wnt4 Signaling Functions In Diverse Tumor Typesmentioning

confidence: 99%

Estrogen controls mTOR signaling and mitochondrial function via WNT4 in lobular carcinoma cells

Shackleford

Bordeaux

et al. 2019

Preprint

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Twitter: @mjsikoraAuthors' contributions MJS, DMR, and SO conceived of the project and experiments. MJS, DMR, EKB, and HMH designed and performed experiments. MJS and DMR developed models for the project. All authors contributed to data analysis and interpretation. MJS wrote the draft manuscript; all authors read and revised the manuscript and have read and approved of this version of the manuscript. AbstractInvasive lobular carcinoma of the breast (ILC) is strongly estrogen-driven, and represents a unique context for estrogen receptor (ER) signaling. In ILC, ER controls the expression of the Wnt ligand WNT4, which is critical for endocrine response and anti-estrogen resistance, yet signaling mediated by WNT4 is poorly understood. We utilized reverse phase protein array (RPPA) to characterize ER and WNT4-driven signaling in ILC cells, and identified WNT4 as a mediator of downstream mTOR signaling via p70-S6K. Independent of mTOR/p70-S6K, ER and WNT4 control levels of MCL-1, which is associated with mitochondrial function. In this context, knockdown of WNT4 caused accumulation of reactive oxygen species and decreased ATP production that precede cell death. WNT4 regulation of both mTOR signaling and MCL-1 levels was also observed in anti-estrogen resistant models of ILC.Further, we identified that high WNT4 expression is associated with similar mTOR pathway activation in serous ovarian cancer tumors, suggesting that this WNT4 pathway is important in multiple tumor types.The identified downstream pathways represent potential targets to inhibit WNT4 signaling in ovarian cancer and overcome anti-estrogen resistance for patients with ILC.

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Wnt4 is essential to normal mammalian lung development

Cited by 55 publications

References 55 publications

IWP2 impairs the development of porcine somatic cell nuclear transfer embryos via Wnt signaling pathway inactivation

IWP2 impairs the development of porcine somatic cell nuclear transfer embryos via Wnt signaling pathway inactivation

Heterogeneity of Fibroblasts and Myofibroblasts in Pulmonary Fibrosis

Estrogen controls mTOR signaling and mitochondrial function via WNT4 in lobular carcinoma cells

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