Zebrafish prickle, a modulator of noncanonical Wnt/Fz signaling, regulates gastrulation movements.

By M. Veeman, Diane C. Slusarski, A. Kaykas, Sarah Louie, R. Moon. Current Biology, 2003

977 citations recorded by the source corpus.

In addition to the canonical Wnt/beta-catenin signaling pathway, at least two noncanonical Wnt/Fz pathways have been described: the planar cell polarity (PCP) pathway in Drosophila [1] and the Wnt/calcium pathway in vertebrate embryos [2]. Recent work suggests that a vertebrate pathway homologous to the PCP pathway acts to regulate the convergent extension movements of gastrulation [3-7]. To further test this hypothesis, we have identified two zebrafish homologs of the Drosophila PCP gene prickle (pk) [8], both of which show discrete and dynamic expression patterns during gastrulation. Both gain and loss of pk1 function cause defects in convergent extension. Pk1 localizes to both the cytoplasm and the cell membrane, and its normal localization is partially dependent on its C-terminal prenylation motif. At the cell membrane, Pk1 is frequently localized asymmetrically around the cell and can colocalize with the signaling molecule Dishevelled (Dsh). In overexpression assays, Pk1 is able to activate AP-1-mediated transcription and inhibit activation of Wnt/beta-catenin signaling. Like noncanonical Wnts [9-10], overexpression of Pk1 increases the frequency of calcium transients in zebrafish blastulae. Our results support the idea that a vertebrate PCP pathway regulates gastrulation movements and suggest that there is overlap between the PCP and Wnt/calcium pathways.

Subfields: Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/242b8e6564b564ea6c2e8b580422349d53b2957c

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Citations in the corpus

• R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/β-catenin signaling (2011, background): “Using a β-catenin–responsive reporter assay (27), we examined the effect of RSPO treatment on Wnt/ β-catenin signaling in HEK293T cells overexpressing LGR4 or LGR5 in the presence of exogenous Wnt3a.”
• DISC1 regulates neural progenitor proliferation via modulation of GSK3β/β-catenin signaling (2009, background): “Together, these results implicate DISC1 in GSK3b/b-catenin signaling pathways and provide a framework for understanding how alterations in this pathway may contribute to the etiology of psychiatric disorders.”
• Precise Regulation of Porcupine Activity Is Required for Physiological Wnt Signaling (2012, methodology): “Super8xTopflash reporter was a gift from Randy Moon (37). pGK-WNT3A plasmid was provided by Karl Willert.”
• Fragile X Mental Retardation Protein Regulates Proliferation and Differentiation of Adult Neural Stem/Progenitor Cells (2010, methodology): “To confirm that loss of Fmrp led to the deficit in the Wnt signaling pathway, we used a well-characterized luciferase reporter system for monitoring the activity of the Wnt signaling pathway [26,49].”
• Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. (2012, background): “This revealed that Pk1 colocalized extensively with cortical F-actin, as previously found by Veeman et al. (2003), and was aligned along the nonprotrusive cell membrane (Figure 3B).”
• Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast (2011, methodology): “We measured the activity of b-catenin-dependent canonical Wnt signaling pathway using the TOPFlash b-catenin/TCF-LEF reporter assay (Veeman et al., 2003).”
• Functional redundancy of GSK-3α and GSK-3β in wnt/β-catenin signaling shown by using an allelic series of embryonic stem cell lines (2007, methodology): “The TCF reporter plasmids super8XTOPFlash and super8XFOPFlash (Veeman et al., 2003) (obtained from Randall Moon.”
• Surrogate Wnt agonists that phenocopy canonical Wnt/β-catenin signaling (2017, neutral): “HEK293 cells stably transfected with the STF plasmid encoding the firefly luciferase reporter under the control of a minimal promoter, and a con-catemer of 7 LEF/TCF binding sites 32 , were obtained from J. Nathans.”