Wnt Signals Organize Synaptic Prepattern and Axon Guidance through the Zebrafish unplugged/MuSK Receptor

Jing, Lili; Lefebvre, Julie L.; Gordon, Laura R.; Granato, Michael

doi:10.1016/j.neuron.2008.12.025

Cited by 169 publications

(243 citation statements)

References 67 publications

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“…APC, an adaptor downstream of Dvl in the canonical pathway, was shown to regulate AChR clustering (Wang et al, 2003). In zebrafish, Wnt11r binds to unplugged, the zebrafish MuSK homolog, to guide motor axons (Jing et al, 2009). In mammalian muscle cells, five Wnts (Wnt9a, Wnt9b, Wnt10b, Wnt11 and Wnt16), presumably by direct binding to MuSK, are able to stimulate AChR clustering, in a manner dependent on LRP4 .…”

Section: Wnt Signaling or Cadherin Signaling In Nmj Formationmentioning

confidence: 99%

β-Catenin gain of function in muscles impairs neuromuscular junction formation

Barik

et al. 2012

Development

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Section: Wnt Signaling or Cadherin Signaling In Nmj Formationmentioning

confidence: 99%

β-Catenin gain of function in muscles impairs neuromuscular junction formation

Barik

et al. 2012

Development

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“…Wnt7a also promotes postsynaptic development of excitatory neurons in the hippocampus (Ciani et al, 2011). At the mammalian neuromuscular junction, Wnt activates postsynaptic clustering of acetylcholine receptors and can be provided by either the innervating motor neuron (Henriquez et al, 2008) or by nearby non-neuronal tissues (Jing et al, 2009). In these instances, the Wnt signal is transduced by non-canonical pathways that act locally and apparently do not require transcription (Cerpa et al, 2008;Miech et al, 2008;Purro et al, 2008;Sahores et al, 2010;Budnik and Salinas, 2011).…”

Section: Wnt Signaling Regulates Synaptic Choicementioning

confidence: 99%

UNC-4 antagonizes Wnt signaling to regulate synaptic choice in the C. elegans motor circuit

et al. 2012

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SUMMARYCoordinated movement depends on the creation of synapses between specific neurons in the motor circuit. In C. elegans, this important decision is regulated by the UNC-4 homeodomain protein. unc-4 mutants are unable to execute backward locomotion because VA motor neurons are mis-wired with inputs normally reserved for their VB sisters. We have proposed that UNC-4 functions in VAs to block expression of VB genes. This model is substantiated by the finding that ectopic expression of the VB gene ceh-12 (encoding a homolog of the homeodomain protein HB9) in unc-4 mutants results in the mis-wiring of posterior VA motor neurons with VB-like connections. Here, we show that VA expression of CEH-12 depends on a nearby source of the Wnt protein EGL-20. Our results indicate that UNC-4 prevents VAs from responding to a local EGL-20 cue by disabling a canonical Wnt signaling cascade involving the Frizzled receptors MIG-1 and MOM-5. CEH-12 expression in VA motor neurons is also opposed by a separate pathway that includes the Wnt ligand LIN-44. This work has revealed a transcriptional mechanism for modulating the sensitivity of specific neurons to diffusible Wnt ligands and thereby defines distinct patterns of synaptic connectivity. The existence of comparable Wnt gradients in the vertebrate spinal cord could reflect similar roles for Wnt signaling in vertebrate motor circuit assembly.

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“…The Wnt/PCP pathway also regulates axon development and vertebrate homologs of the Drosophila proteins, such as Flamingo, Frizzled, Dishevelled and Stbm, have different roles in axon guidance (Wang et al, 2002;Lyuksyutova et al, 2003;Tissir et al, 2005;Zhou et al, 2008;Jing et al, 2009;Fenstermaker et al, 2010;Shafer et al, 2011). Interestingly, Drosophila studies show that Wnt/PCP factors (such as Flamingo/Starry night) can function independently of other 'core' components to regulate axon and dendrite patterning (Gao et al, 2000;Senti et al, 2003;Steinel and Whitington, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, timing studies suggest that some PCPdependent events occur early, prior to obvious PCP protein asymmetry Classen et al, 2005;Strutt and Strutt, 2007;Doyle et al, 2008). Nonetheless, whether as a basis of the cause or the consequence of tissue polarization, vertebrate PCP proteins also show subcellular asymmetry in polarized tissues (Wang et al, 2005;Montcouquiol et al, 2006;Wang et al, 2006;Deans et al, 2007;Jones and Chen, 2007;Qian et al, 2007;Wang and Nathans, 2007;Devenport and Fuchs, 2008;Sugiyama et al, 2010), suggesting that PCP protein asymmetry is a conserved feature in tissue polarity.The Wnt/PCP pathway also regulates axon development and vertebrate homologs of the Drosophila proteins, such as Flamingo, Frizzled, Dishevelled and Stbm, have different roles in axon guidance (Wang et al, 2002;Lyuksyutova et al, 2003;Tissir et al, 2005;Zhou et al, 2008;Jing et al, 2009;Fenstermaker et al, 2010;Shafer et al, 2011). Interestingly, Drosophila studies show that Wnt/PCP factors (such as Flamingo/Starry night) can function independently of other 'core' components to regulate axon and dendrite patterning (Gao et al, 2000;Senti et al, 2003;Steinel and Whitington, 2009).…”

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confidence: 99%

Wnt/PCP proteins regulate stereotyped axon branch extension inDrosophila

2012

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SUMMARYBranching morphology is a hallmark feature of axons and dendrites and is essential for neuronal connectivity. To understand how this develops, I analyzed the stereotyped pattern of Drosophila mushroom body (MB) neurons, which have single axons branches that extend dorsally and medially. I found that components of the Wnt/Planar Cell Polarity (PCP) pathway control MB axon branching. frizzled mutant animals showed a predominant loss of dorsal branch extension, whereas strabismus (also known as Van Gogh) mutants preferentially lost medial branches. Further results suggest that Frizzled and Strabismus act independently. Nonetheless, branching fates are determined by complex Wnt/PCP interactions, including interactions with Dishevelled and Prickle that function in a context-dependent manner. Branching decisions are MB-autonomous but non-cell-autonomous as mutant and non-mutant neurons regulate these decisions collectively. I found that Wnt/PCP components do not need to be asymmetrically localized to distinct branches to execute branching functions. However, Prickle axonal localization depends on Frizzled and Strabismus. KEY WORDS: Axon Branching, Planar cell polarity (PCP), DrosophilaWnt/PCP proteins regulate stereotyped axon branch extension in Drosophila Julian Ng* DEVELOPMENT 166As branch formation might involve cell-polarizing mechanisms, I decided to study components of the Wnt/Planar Cell Polarity (PCP) pathway. The Wnt/PCP pathway represents a major class of regulators that control planar cell polarity (also termed tissue polarity or planar polarity). This has been extensively studied in Drosophila patterning of the adult cuticle in the wing, abdomen and notum, in the Drosophila eye and in sensory hair cells of the inner ear in mice (Klein and Mlodzik, 2005;Jones and Chen, 2007;Wang and Nathans, 2007;Strutt, 2009;Vladar et al., 2009). The Wnt/PCP pathway acts to orient cells along an axis so that all cells exhibit a grouped polarity. These genes can act both cellautonomously (intracellularly) and non-autonomously (intercellularly between neighboring cells).Despite extensive studies, how they function is unclear and several distinct models are proposed, based principally on Drosophila results (Klein and Mlodzik, 2005;Lawrence et al., 2007;Strutt and Strutt, 2009;Vladar et al., 2009). One key finding is that a seven-pass transmembrane protein Frizzled (Fz) is essential (Gubb and Garcia-Bellido, 1982;Vinson and Adler, 1987;Vinson et al., 1989). How Fz regulates tissue polarity is much debated. One model suggests 'core' components of the Wnt/PCP pathway act to localize Fz asymmetrically within cells (Strutt, 2001;Strutt, 2003;Klein and Mlodzik, 2005;Strutt and Strutt, 2009;Vladar et al., 2009). Acting as an anti-Fz factor, the four-pass transmembrane protein Strabismus (Stbm, also known as Van Gogh or Vang) is thought to act intracellularly to restrict Fz localization to the pole opposite of Stbm (Jenny et al., 2003;Amonlirdviman et al., 2005;Klein and Mlodzik, 2005;Vladar et al., 2009). Interestingly, in g...

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Wnt Signals Organize Synaptic Prepattern and Axon Guidance through the Zebrafish unplugged/MuSK Receptor

Cited by 169 publications

References 67 publications

β-Catenin gain of function in muscles impairs neuromuscular junction formation

β-Catenin gain of function in muscles impairs neuromuscular junction formation

UNC-4 antagonizes Wnt signaling to regulate synaptic choice in the C. elegans motor circuit

Wnt/PCP proteins regulate stereotyped axon branch extension inDrosophila

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