IGF antagonizes the Wnt/β-Catenin pathway and promotes differentiation of extra-embryonic endoderm

Schlupf, Judith; Steinbeißer, Herbert

doi:10.1016/j.diff.2014.07.003

Cited by 15 publications

(12 citation statements)

References 69 publications

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“…Because IFE stem cells are maintained by autocrine Wnt signalling 8 , Sfrp1 may directly repress autocrine Wnt signalling to induce Axin2 + -to-Tbx3 + cell transition. Recent studies have reported an antagonistic role of IGF signalling against the Wnt pathway 38 , 39 , implying a latent function of Igfbp2 in Wnt inhibition to induce Axin2 + -to-Tbx3 + cell transition. However, these results are apparently inconsistent with a previous study demonstrating that loss of Wnt signalling (β-catenin deletion) in Axin2 -expressing cells results in repression of their proliferation in the IFE basal layer 8 .…”

Section: Discussionmentioning

confidence: 99%

Tbx3-dependent amplifying stem cell progeny drives interfollicular epidermal expansion during pregnancy and regeneration

et al. 2017

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The skin surface area varies flexibly in response to body shape changes. Skin homeostasis is maintained by stem cells residing in the basal layer of the interfollicular epidermis. However, how the interfollicular epidermal stem cells response to physiological body shape changes remains elusive. Here, we identify a highly proliferative interfollicular epidermal basal cell population in the rapidly expanding abdominal skin of pregnant mice. These cells express Tbx3 that is necessary for their propagation to drive skin expansion. The Tbx3+ basal cells are generated from Axin2+ interfollicular epidermal stem cells through planar-oriented asymmetric or symmetric cell divisions, and express transit-amplifying cell marker CD71. This biased division of Axin2+ interfollicular epidermal stem cells is induced by Sfrp1 and Igfbp2 proteins secreted from dermal cells. The Tbx3+ basal cells promote wound repair, which is enhanced by Sfrp1 and Igfbp2. This study elucidates the interfollicular epidermal stem cell/progeny organisation during pregnancy and suggests its application in regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

Tbx3-dependent amplifying stem cell progeny drives interfollicular epidermal expansion during pregnancy and regeneration

et al. 2017

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“…These results indicated that reducing the message encoding the FZD7 receptor using an siRNA approach reduced DAB2 signal, but did not have a (Shibamoto et al 2004). Another defined mechanism involves IGF, which induces Axin2 and stabilizes AXIN1 (Schlupf and Steinbeisser 2014). Thus, there are several mechanisms in place, but other inhibitors of WNT signaling may also be induced in response to activated WNT6 signaling.…”

Section: Fzd7 Knockdown Does Not Inhibit Ra-induced Primitive Endodermentioning

confidence: 90%

“…In addition to WNT6 acting through a FZD receptor to regulate genes required for the differentiation to PrE, mechanisms are in place to attenuate the canonical WNT signal for these cells to differentiate into PE and VE (LaMonica et al 2009;Schlupf and Steinbeisser 2014;Shibamoto et al 2004). There is evidence that F9 cells express intracellular and extracellular inhibitors of WNT signaling during differentiation (Shibamoto et al 2004;Zhuang et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Frizzledgene expression and negative regulation of canonical WNT–β-catenin signaling in mouse F9 teratocarcinoma cells

Golenia

Gatie

Kelly

2017

Biochem. Cell Biol.

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Mouse F9 cells differentiate into primitive endoderm (PrE) following the activation of the canonical WNT/β-catenin pathway. The upregulation of Wnt6 and activation of β-catenin-TCF/LEF-dependent transcription is known to accompany differentiation, but the Frizzled (FZD) receptor responsible for transducing the WNT6 signal is not known. Eight of the ten Fzd genes were found to be expressed in F9 cells, with Fzd7 being the most highly expressed, and chosen for further analysis. To alter steady-state Fzd7 levels and test the effect this has on differentiation, siRNA and overexpression approaches were used to knockdown and ectopically express the Fzd7 message, respectively. siRNA knock down of Fzd7 resulted in reduced DAB2 levels, and the overexpression activated a TCF-LEF reporter, but neither approach affected differentiation. Our focus turned to how canonical WNT6 signaling was attenuated to allow PrE cells to form PE. Dkk1, encoding a WNT antagonist, was examined and results showed that its expression increased in F9 cells treated with RA or overexpressing Wnt6. F9 cells overexpressing human DKK1 or treated with DKK1-conditioned medium and then treated with RA failed to differentiate, indicating that a negative feedback loop involving WNT6 and DKK1 attenuates canonical WNT/β-catenin signaling, thereby allowing PE cells to differentiate.

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“…Between spleen group and kidney group, ANP increases calcitonin gene-related peptide (CGRP) within human circulation [144]. Between kidney group and heart group, calcitonin increases concentration of IGF [145], and IGF signaling antagonizes the Wnt pathway [146].…”

Section: The Interrelationships Among Groups Of Moleculesmentioning

confidence: 99%

The closed-loop pathways of signaling molecules

Liu

2017

Preprint

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The pathways of signaling molecules are important to understanding how signaling molecules regulate physiological function and also in predicting the pathological development which is important to therapeutic strategy, however the thorough knowledge of these pathways is still lack. In this paper, we used the big data concept to analyze the pathways of signaling molecules and categorize these molecules into five groups according to their origin and effect on the five organs of heart-spleen-lung-kidney-liver. Heart group includes IGF, Ang and Mg; spleen group includes ANP, aldosterone, retinoic acid and ghrelin; lung group includes FGF7, VEGF, ascorbic acid and HIF; kidney group includes calcitonin, PTHrP, Wnt and NO; and liver group includes EPO, renin, SOD, AKR and GSH.We found that each group of molecules have assisting effect on the other organ in the order of heart-spleen-lung-kidney-liver-heart, and have regulating effect on the other organ in the order of heart-lung-liver-spleen-kidney-heart. Moreover, the pathways of molecules of each group also follow these two arrangements, in which the pathways of molecules form a closed-loop that may lead to new therapeutic strategies.

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IGF antagonizes the Wnt/β-Catenin pathway and promotes differentiation of extra-embryonic endoderm

Cited by 15 publications

References 69 publications

Tbx3-dependent amplifying stem cell progeny drives interfollicular epidermal expansion during pregnancy and regeneration

Tbx3-dependent amplifying stem cell progeny drives interfollicular epidermal expansion during pregnancy and regeneration

Frizzledgene expression and negative regulation of canonical WNT–β-catenin signaling in mouse F9 teratocarcinoma cells

The closed-loop pathways of signaling molecules

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