Wnt/PCP Instructions for Cilia in Left-Right Asymmetry

Wu, Jun; Mlodzik, Marek

doi:10.1016/j.devcel.2017.02.023

Cited by 10 publications

(8 citation statements)

References 10 publications

(20 reference statements)

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“…Wnt5a acts both as a suppressor and an inducer in different types of tumors ( 12 , 23 – 26 ). The Wnt/planar cell polarity (PCP) pathway triggered by Wnt5a activates small Rho-GTPases and reassembles the cytoskeletal architecture and cellular polarity during embryo development and pathological processes ( 27 – 29 ). In our previous studies, we found that Wnt5a stimulated the migration of breast cancer cells via Rho signaling pathways ( 21 , 30 ).…”

Section: Discussionmentioning

confidence: 99%

Daam1 activates RhoA to regulate Wnt5a‑induced glioblastoma cell invasion

Liu

Yan

et al. 2017

Oncol Rep

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The signaling pathway of dishevelled-associated activator of morphogenesis 1 (Daam1) triggered by Wnt5a drives cell movement and migration during breast cancer metastasis. However, Wnt5a signaling in glioblastoma progression remains poorly defined. Wnt5a expression and activations of RhoA, Cdc42, and Rac1 were detected in human glioblastoma tissues by using ELISA assays and small G-protein activation assays, respectively. The cell invasion rate and Daam1 activation of glioblastoma U251 and T98MG cells were determined by cell invasion assays and pull-down assays, respectively. According to our experiments, Wnt5a expression and RhoA activation were upregulated in invasive glioblastoma tissues, with a significant positive correlation between them. Wnt5a activated Daam1 and RhoA, and subsequently promoted the invasion of glioblastoma U251 and T98MG cells. This process was abolished by secreted frizzled-related protein 2 (sFRP2), an antagonist that directly binds to Wnt5a. Specific small interfering RNA (siRNA) targeting Daam1 markedly inhibited Wnt5a-induced RhoA activation, stress fiber formation and glioblastoma cell invasion. CCG-1423, a RhoA inhibitor, decreased Wnt5a-induced stress fiber formation and glioblastoma cell invasion. Finally, siRNA targeting Daam1 or CCG-1423 treatment did not alter the cell proliferation of glioblastoma U251 and T98MG cells. We thus concluded that Wnt5a promoted glioblastoma cell invasion via Daam1/RhoA signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Daam1 activates RhoA to regulate Wnt5a‑induced glioblastoma cell invasion

Liu

Yan

et al. 2017

Oncol Rep

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“…A key question is the extracellular cue that aligns the core PCP proteins with the global tissue axes. Although Wnt ligands have been implicated, a definitive link between them and PCP signaling has been difficult to establish [20,21,53]. Our work showing that Wnt5 and Vang act together to direct the orientation of nascent glomeruli adds to two other reports [54,55] that Wnt proteins play instructive roles in PCP signaling.…”

Section: Plos Geneticsmentioning

confidence: 62%

Interplay between axonal Wnt5-Vang and dendritic Wnt5-Drl/Ryk signaling controls glomerular patterning in the Drosophila antennal lobe

et al. 2020

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Despite the importance of dendritic targeting in neural circuit assembly, the mechanisms by which it is controlled still remain incompletely understood. We previously showed that in the developing Drosophila antennal lobe, the Wnt5 protein forms a gradient that directs the~45r otation of a cluster of projection neuron (PN) dendrites, including the adjacent DA1 and VA1d dendrites. We report here that the Van Gogh (Vang) transmembrane planar cell polarity (PCP) protein is required for the rotation of the DA1/VA1d dendritic pair. Cell type-specific rescue and mosaic analyses showed that Vang functions in the olfactory receptor neurons (ORNs), suggesting a codependence of ORN axonal and PN dendritic targeting. Loss of Vang suppressed the repulsion of the VA1d dendrites by Wnt5, indicating that Wnt5 signals through Vang to direct the rotation of the DA1 and VA1d glomeruli. We observed that the Derailed (Drl)/Ryk atypical receptor tyrosine kinase is also required for the rotation of the DA1/VA1d dendritic pair. Antibody staining showed that Drl/Ryk is much more highly expressed by the DA1 dendrites than the adjacent VA1d dendrites. Mosaic and epistatic analyses showed that Drl/Ryk specifically functions in the DA1 dendrites in which it antagonizes the Wnt5-Vang repulsion and mediates the migration of the DA1 glomerulus towards Wnt5. Thus, the nascent DA1 and VA1d glomeruli appear to exhibit Drl/Ryk-dependent biphasic responses to Wnt5. Our work shows that the final patterning of the fly olfactory map is the result of an interplay between ORN axons and PN dendrites, wherein converging preand postsynaptic processes contribute key Wnt5 signaling components, allowing Wnt5 to orient the rotation of nascent synapses through a PCP mechanism.

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“…Wnt ligands control noncanonical Wnt pathways, including the PCP pathway (Wnt/PCP pathway) (Wu and Mlodzik, 2017;Yang and Mlodzik, 2015). Wingless (Wg) and DWnt4 provide longrange directional information for PCP and control the orientation of hairs on the wing and in the retina (Wu et al, 2013).…”

Section: Introductionmentioning

confidence: 99%