Mapping Wnt/β-catenin signaling during mouse development and in colorectal tumors

Maretto, Silvia; Cordenonsi, Michelangelo; Dupont, Sirio; Braghetta, Paola; Broccoli, Vania; Hassan, A. Bassim; Volpin, Dino; Bressan, Giorgio M.; Piccolo, Stefano

doi:10.1073/pnas.0434590100

Cited by 740 publications

(892 citation statements)

References 41 publications

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“…Wnt-responsive luciferase reporter Bat-luc, Axin1-Myc, Axin2-Myc, and Wnt3a-Myc constructs have been described. (42)(43)(44) Mouse LRP8 shRNAs (LRP8-1, TRCN0000177833; LRP8-2, TRCN0000176636) lentiviral transduction particles were purchased from Sigma Mission Library (St. Louis, MO, USA). All constructions were confirmed by DNA sequencing.…”

Section: Plasmid Constructsmentioning

confidence: 99%

LRP8 mediates Wnt/β-catenin signaling and controls osteoblast differentiation

Zhang

et al. 2012

Journal of Bone and Mineral Research

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The Wnt/b-catenin signaling pathway plays a pivotal role in regulating osteoblast differentiation and bone formation. Here, we identify low-density lipoprotein (LDL) receptor-related protein 8 (LRP8) as a positive regulator of Wnt/b-catenin signaling. In a small interfering RNA (siRNA) screen, LRP8 was shown to be required for Wnt/b-catenin-induced transcriptional reporter activity. We found that ectopic expression of LRP8 increased Wnt-induced transcriptional responses, and promoted Wnt-induced b-catenin accumulation. Moreover, knockdown of LRP8 resulted in a decrease in b-catenin levels and suppression of Wnt/b-catenin-induced Axin2 transcription. Functional studies in KS483 osteoprogenitor cells showed that LRP8 depletion resulted in impaired activation of endogenous Wnt-induced genes and decreased osteoblast differentiation and mineralization, whereas LRP8 ectopic expression had the opposite effect. These results identify LRP8 as a novel positive factor of canonical Wnt signaling pathway and show its involvement in Wnt-induced osteoblast differentiation. ß

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Section: Plasmid Constructsmentioning

confidence: 99%

LRP8 mediates Wnt/β-catenin signaling and controls osteoblast differentiation

Zhang

et al. 2012

Journal of Bone and Mineral Research

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“…Indeed, mounting evidence gathered from functional studies of either Wnt ligands or their downstream signaling components, including the complex of receptors, have shown that in the developing brain Wnt signaling participates in patterning the midbrain-hindbrain boundary, which later on gives rise to the brainstem and the cerebellum ( McMahon and Bradley, 1990; Thomas and Capecchi, 1990;Thomas et al, 1991;McMahon et al, 1992;Hall et al, 2000), and forebrain derivatives such as the cerebral cortex, hippocampal formation and the amygdala (Grove et al, 1998;Lako et al, 1998;Lee et al, 2000;Houart et al, 2002;Maretto et al, 2003;Abu-Khalil et al, 2004;Zhou et al, 2004). Remarkably, embryonic transgenic mice expressing active stabilized forms of b-catenin in neuronal precursor cells developed gross enlargements of the cerebral cortex, hippocampus and amygdala Walsh, 2002, 2003).…”

Section: Wnt Signaling and Autismmentioning

confidence: 99%

The ups and downs of Wnt signaling in prevalent neurological disorders

2006

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In order to function properly, the brain must be wired correctly during critical periods in early development. Mistakes in this process are hypothesized to occur in disorders like autism and schizophrenia. Later in life, signaling pathways are essential in maintaining proper communication between neuronal and non-neuronal cells, and disrupting this balance may result in disorders like Alzheimer's disease. The Wnt/b-catenin pathway has a well-established role in cancer. Here, we review recent evidence showing the involvement of Wnt/b-catenin signaling in neurodevelopment as well as in neurodegenerative diseases. We suggest that the onset/development of such pathological conditions may involve the additive effect of genetic variation within Wnt signaling components and of molecules that modulate the activity of this signaling cascade.

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“…Studies making use of a canonical pathway reporter in mice, in which multimerized Lef/Tcf binding sites control expression of the β-galactosidase reporter (the so-called Bat-Gal mouse), as well as examination of the mRNA for a general β-catenin target gene, Axin2, showed little, if any, β-catenin activity in the mesenchyme, while there was high activity in the UB and collecting ducts [60][61][62] (Fig. 5).…”

Section: Pathway Usage In Renal Vesicle Formationmentioning

confidence: 99%

Molecular regulation of kidney development: is the answer blowing in the Wnt?

2007

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Development of the metanephric kidney is a complicated process regulated by reciprocal signals from the ureteric bud and the metanephric mesenchyme that regulate tubule formation and epithelial branching morphogenesis. Over the past several years, several studies have suggested that Wnt signaling is involved in multiple aspects of normal kidney development as well as injury response and cancer progression. We will review these data here.

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Mapping Wnt/β-catenin signaling during mouse development and in colorectal tumors

Cited by 740 publications

References 41 publications

LRP8 mediates Wnt/β-catenin signaling and controls osteoblast differentiation

LRP8 mediates Wnt/β-catenin signaling and controls osteoblast differentiation

The ups and downs of Wnt signaling in prevalent neurological disorders

Molecular regulation of kidney development: is the answer blowing in the Wnt?

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