R-spondin signalling is essential for the maintenance and differentiation of mouse nephron progenitors

Vidal, Valérie; Motamedi, Fariba Jian; Rekima, Samah; Gregoire, Elodie P.; Szenker‐Ravi, Emmanuelle; Leushacke, Marc; Reversade, Bruno; Chaboissier, Marie-Christine; Schedl, Andreas

doi:10.7554/elife.53895

Cited by 19 publications

(11 citation statements)

References 46 publications

(44 reference statements)

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“…In the present study, we showed the paracrine function of Rspo3 for muscle fibre type determination using an in vitro experiment. In general, Rspo3 is recognised ubiquitously as being expressed throughout the developing body for proper organ formation 43 – 45 . Furthermore, Rspo3 is required for maintaining gastric epithelial stem cells in response to H. pylori infection 46 , for epithelial regeneration in the colon 47 , and for preventing the formation of anti-inflammatory interstitial macrophages 48 .…”

Section: Discussionmentioning

confidence: 99%

R-spondin3 is a myokine that differentiates myoblasts to type I fibres

Mita

Zhu

Furuichi

et al. 2022

Sci Rep

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Muscle fibres are broadly categorised into types I and II; the fibre-type ratio determines the contractile and metabolic properties of skeletal muscle tissue. The maintenance of type I fibres is essential for the prevention of obesity and the treatment of muscle atrophy caused by type 2 diabetes or unloading. Some reports suggest that myokines are related to muscle fibre type determination. We thus explored whether a myokine determines whether satellite cells differentiate to type I fibres. By examining the fibre types separately, we identified R-spondin 3 (Rspo3) as a myokine of interest, a secreted protein known as an activator of Wnt signalling pathways. To examine whether Rspo3 induces type I fibres, primary myoblasts prepared from mouse soleus muscles were exposed to a differentiation medium containing the mouse recombinant Rspo3 protein. Expression of myosin heavy chain (MyHC) I, a marker of type I fibre, significantly increased in the differentiated myotubes compared with a control. The Wnt/β-catenin pathway was shown to be the dominant signalling pathway which induces Rspo3-induced MyHC I expression. These results revealed Rspo3 as a myokine that determines whether satellite cells differentiate to type I fibres.

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Section: Discussionmentioning

confidence: 99%

R-spondin3 is a myokine that differentiates myoblasts to type I fibres

Mita

Zhu

Furuichi

et al. 2022

Sci Rep

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“…7 E,F; ) ( Karner et al, 2011 ; Lu et al, 2009 ; Vidal et al, 2020 ). Such molecular changes in the postnatal UB likely thus provide a favorable environment for sustained NP self-renewal beyond P2/P3.…”

Section: Discussionmentioning

confidence: 99%

Postnatal prolongation of mammalian nephrogenesis by excess fetal GDNF

Kurtzeborn

Kupari

et al. 2021

Development

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Nephron endowment, defined during the fetal period, dictates renal and related cardiovascular health throughout life. We show here that, despite its negative effects on kidney growth, genetic increase of GDNF prolongs the nephrogenic program beyond its normal cessation. Multi-stage mechanistic analysis revealed that excess GDNF maintains nephron progenitors and nephrogenesis through increased expression of its secreted targets and augmented WNT signaling, leading to a two-part effect on nephron progenitor maintenance. Abnormally high GDNF in embryonic kidneys upregulates its known targets but also Wnt9b and Axin2, with concomitant deceleration of nephron progenitor proliferation. Decline of GDNF levels in postnatal kidneys normalizes the ureteric bud and creates a permissive environment for continuation of the nephrogenic program, as demonstrated by morphologically and molecularly normal postnatal nephron progenitor self-renewal and differentiation. These results establish that excess GDNF has a bi-phasic effect on nephron progenitors in mice, which can faithfully respond to GDNF dosage manipulation during the fetal and postnatal period. Our results suggest that sensing the signaling activity level is an important mechanism through which GDNF and other molecules contribute to nephron progenitor lifespan specification.

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“…In addition, it has been shown that LGR6 is required for human fallopian organoid development (Kessler et al, 2015). We and others demonstrated that Lgr4 expresses in a variety of tissues and plays a significant role in amplifying the WNT/CTNNB1 signal in multiple tissues and organs, like hair follicles (Zak et al, 2016), ovaries (Pan et al, 2014), kidneys (Vidal et al, 2020), intestine (Liu et al, 2013), male reproductive tract (Qian et al, 2013), uterus (Sone et al, 2013), and many others (Wang et al, 2013;Han et al, 2014;Planas-Paz et al, 2016). However, to date, the role of LGR4 in the oviduct/fallopian tube is still obscure.…”

Section: Introductionmentioning

confidence: 93%

Lgr4 Regulates Oviductal Epithelial Secretion Through the WNT Signaling Pathway

Tan

Zhang

et al. 2021

Front. Cell Dev. Biol.

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The WNT signaling pathway plays a crucial role in oviduct/fallopian development. However, the specific physiological processes regulated by the WNT pathway in the fallopian/oviduct function remain obscure. Benefiting from the Lgr4 knockout mouse model, we report the regulation of oviduct epithelial secretion by LGR4. Specifically, the loss of Lgr4 altered the mouse oviduct size and weight, severely reduced the number of oviductal epithelial cells, and ultimately impaired the epithelial secretion. These alterations were mediated by a failure of CTNNB1 protein accumulation in the oviductal epithelial cytoplasm, by the modulation of WNT pathways, and subsequently by a profound change of the gene expression profile of epithelial cells. In addition, selective activation of the WNT pathway triggered the expression of steroidogenic genes, like Cyp11a1 and 3β-Hsd1, through the activation of the transcriptional factor NR5A2 in an oviduct primary cell culture system. As demonstrated, the LGR4 protein modulates a WNT-NR5A2 signaling cascade facilitating epithelial secretory cell maturation and steroidogenesis to safeguard oviduct development and function in mice.

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R-spondin signalling is essential for the maintenance and differentiation of mouse nephron progenitors

Cited by 19 publications

References 46 publications

R-spondin3 is a myokine that differentiates myoblasts to type I fibres

R-spondin3 is a myokine that differentiates myoblasts to type I fibres

Postnatal prolongation of mammalian nephrogenesis by excess fetal GDNF

Lgr4 Regulates Oviductal Epithelial Secretion Through the WNT Signaling Pathway

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