Wnt Signaling and Stem Cell Control

Nusse, Roel; Fuerer, Christophe; Ching, Wendy; Harnish, K.; Logan, Cheryl A.; Zeng, Angela; Berge, Derk ten; Kalani, Yashar

doi:10.1101/sqb.2008.73.035

Cited by 306 publications

(282 citation statements)

References 73 publications

(87 reference statements)

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“…Several recent studies in rodents have elucidated the role of Wnt/β-catenin signaling in oval cell activation and proliferation. Wnt/ β-catenin signaling is induced in the livers of mice exposed to DDC, and oval cells isolated from DDC-exposed livers display nuclear localization of β-catenin in response to Wnt3a stimulation [32] . In rats, Wnt/β-catenin signaling is also activated by 2AAF/PH [33] .…”

Section: Discussionmentioning

confidence: 99%

GSK-3β suppresses the proliferation of rat hepatic oval cells through modulating Wnt/β-catenin signaling pathway

Xie

Zhong

et al. 2015

Acta Pharmacol Sin

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Aim: Glycogen synthase kinase 3β (GSK-3β) plays a crucial role in hepatic biology, including liver development, regeneration, proliferation and carcinogenesis. In this study we investigated the role of GSK-3β in regulation of growth of hepatic oval cells in vitro and in liver regeneration in partially hepatectomized rats. Methods: WB-F344 cells, the rat hepatic stem-like epithelial cells, were used as representative of oval cells. Cell viability was examined using a WST-8 assay. The cells were transfected with a recombinant lentivirus expressing siRNA against GSK-3β (GSK3βRNAiLV) or a lentivirus that overexpressed GSK-3β (GC-GSK-3βLV). Adult rats underwent partial (70%) hepatectomy, and liver weight and femur length were measured at d 7 after the surgery. The expression of GSK-3β, phospho-Ser 9 -GSK-3β, β-catenin and cyclin D1 was examined with immunoblotting assays or immunohistochemistry. Results: Treatment of WB-F344 cells with the GSK-3β inhibitor SB216763 (5 and 10 µmol/L) dose-dependently increased the levels of phospho-Ser 9 -GSK-3β, but not the levels of total GSK-3β, and promoted the cell proliferation. Knockout of GSK-3β with GSK-3βRNAiLV increased the cell proliferation, whereas overexpression of GSK-3β with GC-GSK-3βLV decreased the proliferation. Both SB216763 and GSK-3βRNAiLV significantly increased the levels of β-catenin and cyclin D1 in the cells, whereas GSK-3β overexpression decreased their levels. In rats with a partial hepatectomy, administration of SB216763 (2 mg/kg, ip) significantly increased the number of oval cells, the levels of phospho-Ser 9 -GSK-3β, β-catenin and cyclin D1 in liver, as well as the ratio of liver weight to femur length at d 7 after the surgery. Conclusion: GSK-3β suppresses the proliferation of hepatic oval cells by modulating the Wnt/β-catenin signaling pathway.

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Section: Discussionmentioning

confidence: 99%

GSK-3β suppresses the proliferation of rat hepatic oval cells through modulating Wnt/β-catenin signaling pathway

Xie

Zhong

et al. 2015

Acta Pharmacol Sin

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“…emigrating from the dorsal neural tube. For reviews introducing the different signaling pathways see : Shh, [51]; RA, [52]; Wnt, [53]; TGF superfamily, [54] …”

Section: Discussionmentioning

confidence: 99%

Stage- and area-specific control of stem cells in the developing nervous system

Falk¹,

Sommer²

2009

Current Opinion in Genetics & Development

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The spatiotemporal control of proliferation and differentiation in neural stem cells (NSCs) is essential to produce a functional nervous system (NS). Stem cells in different areas and at different time points during development have to produce different types of cells in a precise manner. Recent studies uncovered a plethora of cell extrinsic as well as intrinsic factors that play crucial roles in the area-specific and stage-specific control of NSCs. Moreover, recapitulation of the spatiotemporal specification of NSCs in vitro opens new avenues for future applications. In this review, we have selected some key molecules to discuss the mechanisms underlying the spatiotemporal regulation of NSC development. Stage-and Area-Specific Control of Stem Cells in the Developing Nervous SystemSven Falk 1 , Lukas Sommer Summary of recent advancesThe spatiotemporal control of proliferation and differentiation in neural stem cells ( In this review, we have selected some key molecules to discuss the mechanisms underlying the spatiotemporal regulation of NSC development.

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“…3,4 The WNT signals are transduced through a canonical pathway for cell fate determination and through a non-canonical pathway for control of cell movement and tissue polarity. 6,7,25,26 It is yet unclear, whether WNT10A mediates its function through one or both of these pathways.…”

Section: Discussionmentioning

confidence: 99%

WNT10A missense mutation associated with a complete Odonto-Onycho-Dermal Dysplasia syndrome

et al. 2009

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Wnt signalling is one of a few pathways that are crucial for controlling genetic programs during embryonic development as well as in adult tissues. WNT10A is expressed in the skin and epidermis and it has shown to be critical for the development of ectodermal appendages. A nonsense mutation in WNT10A was recently identified in odonto-onycho-dermal dysplasia (OODD; MIM 257980), a rare syndrome characterised by severe hypodontia, nail dystrophy, smooth tongue, dry skin, keratoderma and hyperhydrosis of palms and soles. We identified a large consanguineous Pakistani pedigree comprising six individuals affected by a complete OODD syndrome. Autozygosity mapping using SNP array analysis showed that the affected individuals are homozygous for the WNT10A gene region. Subsequent mutation screening showed a homozygous c.392C4T transition in exon 3 of WNT10A, which predicts a p.A131V substitution in a conserved a-helix domain. We report here on the first inherited missense mutation in WNT10A with associated ectodermal features.

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Wnt Signaling and Stem Cell Control

Cited by 306 publications

References 73 publications

GSK-3β suppresses the proliferation of rat hepatic oval cells through modulating Wnt/β-catenin signaling pathway

GSK-3β suppresses the proliferation of rat hepatic oval cells through modulating Wnt/β-catenin signaling pathway

Stage- and area-specific control of stem cells in the developing nervous system

WNT10A missense mutation associated with a complete Odonto-Onycho-Dermal Dysplasia syndrome

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