Wnt Signal Transduction in the Cytoplasm

Chen, Tony W.; Wallace, Heather A.; Ahmed, Yashi; Lee, Ethan

doi:10.1002/9781118444122.ch3

Cited by 2 publications

(1 citation statement)

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“…β-Catenin levels are known to both increase and decrease in response to ciliary mutations (Oh and Katsanis, 2013) and our study revealed an increase in β-Catenin levels (Figure 6) indicating an increase in canonical WNT pathway activity. Paradoxically, GSK3β phosphorylation on Ser9 decreased (Figure 6), indicative of a reduction in canonical WNT signaling (Fukumoto et al, 2001; Chen et al, 2014; Llorens-Martín et al, 2014). This suggests that some aspects of these changes originate from sources outside the WNT pathway, e.g., due to cell clumping (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

Roles for IFT172 and Primary Cilia in Cell Migration, Cell Division, and Neocortex Development

Pruski

Yang

et al. 2019

Front. Cell Dev. Biol.

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The cilium of a cell translates varied extracellular cues into intracellular signals that control embryonic development and organ function. The dynamic maintenance of ciliary structure and function requires balanced bidirectional cargo transport involving intraflagellar transport (IFT) complexes. IFT172 is a member of the IFT complex B, and IFT172 mutation is associated with pathologies including short rib thoracic dysplasia, retinitis pigmentosa and Bardet-Biedl syndrome, but how it underpins these conditions is not clear. We used the WIM cell line, derived from embryonic fibroblasts of Wimple mice (carrying homozygous Leu1564Pro mutation in Ift172), to probe roles of Ift172 and primary cilia in cell behavior. WIM cells had ablated cilia and deficiencies in directed migration (electrotaxis), cell proliferation and intracellular signaling. Additionally, WIM cells displayed altered cell cycle progression, with increased numbers of chromatids, highlighting dysfunctional centrosome status. Exposure to a physiological electric field promoted a higher percentage of primary cilia in wild-type cells. Interestingly, in situ hybridization revealed an extensive and dynamic expression profile of Ift172 in both developing and adult mouse cortex. In vivo manipulation of Ift172 expression in germinal regions of embryonic mouse brains perturbed neural progenitor proliferation and radial migration of post-mitotic neurons, revealing a regulatory role of Ift172 in cerebral morphogenesis. Our data suggest that Ift172 regulates a range of fundamental biological processes, highlighting the pivotal roles of the primary cilium in cell physiology and brain development.

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Section: Discussionmentioning

confidence: 99%

Roles for IFT172 and Primary Cilia in Cell Migration, Cell Division, and Neocortex Development

Pruski

Yang

et al. 2019

Front. Cell Dev. Biol.

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Cell‐to‐Cell Signalling in Development: Wnt Signalling

Hoppler

Nakamura

2014

Encyclopedia of Life Sciences

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Wnt signalling is an important cell‐to‐cell signalling mechanism, which is generally conserved among multicellular animals. Wnt signalling operates in the embryo and in adult stem cells, but also in human cancers. Frizzled receptors in the cell membrane are critical functional intermediaries between the extracellular Wnt signal and diverse signal transduction mechanisms that can be activated inside different responding cells. Coreceptors are involved in selecting more specific intracellular signal transduction mechanisms. Frizzled receptors and other Wnt signalling molecules are localised in cells to coordinate planar cell polarity in epithelial tissues and also to regulate morphogenetic movements in embryos. A well‐studied intracellular Wnt signal transduction mechanism promotes stabilisation and nuclear localisation of the protein β‐catenin to regulate transcription of specific target genes by interacting with deoxyribonucleic acid (DNA) ‐binding transcription factor proteins, such as the TCF/LEF proteins. Key Concepts: Wnt signalling functions in the embryo, to regulate stem cells and in disease such as cancer. Wnt signalling mechanisms regulate important cellular processes, such as cell fate specification, cell proliferation, cell differentiation, axon guidance and morphogenesis. Wnt proteins are lipid‐modified secreted signals. Frizzled proteins function as cell membrane receptors for Wnt signals. Wnt/Frizzled signalling activates a network of diverse intracellular signal transduction pathways. One conserved branch of Wnt signal transduction causes stabilisation and nuclear localisation of the protein β‐catenin. Nuclear β‐catenin regulates transcription of specific target genes by interacting with DNA‐binding proteins, such as TCF/LEF proteins. Other, β‐catenin‐independent Wnt signal transduction mechanisms also regulate the cytoskeleton and planar cell polarity. Feedback regulation and cross‐regulation between different Wnt signal transduction branches is characteristic of Wnt signalling.

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Wnt Signal Transduction in the Cytoplasm

Cited by 2 publications

References 146 publications

Roles for IFT172 and Primary Cilia in Cell Migration, Cell Division, and Neocortex Development

Roles for IFT172 and Primary Cilia in Cell Migration, Cell Division, and Neocortex Development

Cell‐to‐Cell Signalling in Development: Wnt Signalling

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