Witzel et al. J Cell Biol. (2006) Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane.

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Presentation transcript:

Witzel et al. J Cell Biol. (2006) Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane

Vertebrate Noncanonical Wnt Signaling Veeman et al. Dev Cell. (2003) PCP signaling play key roles in cell polarization and migration during gastrulation.

Gastrulation movements in zebrafish Solnica-Krezel L. Curr Opin Genet Dev. (2006)

Noncanonical Wnts and Fz regulates cell adhesion Frizzled7 interact with protocadherin which mediate selective cell–cell adhesion. Medina et al. EMBO J. (2004) Ectopic expression of Xwnt-5A leads to decreased Ca 2+ -dependent cell adhesion. Torres et al. J Cell Biol. (1996) Wnt11 controls tissue morphogenesis by modulating E-cadherin- mediated cell cohesion. Ulrich et al. Dev. Cell. (2005)

Wnt11 induces local accumulation of Fz7 at the plasma membrane 5pg mRNA 10pg mRNA20pg mRNA Lyn : membrane-bound kinase - membrane marker

Wnt11 locally accumulates with Fz7 at the plasma membrane Wnt11 producing cell Wnt11 receiving cell

Wnt11-induced Fz7 accumulations form on contacting plasma membranes Wnt11 induces the accumulation of Fz7 on both cells. Fz7-YFP and Fz7-CFP accumulation

Dsh is recruited to Wnt11-induced Fz7 accumulations Wnt11 induces the accumulation of Fz7 together with the Dsh at the plasma membrane in regions of cell contact.

Wnt11-induced accumulations of Fz7 modulate cell contact persistence Wnt11-induced Fz7 accumulations increase the persistence of cell contacts.

Wnt11-induced accumulations of Fz7 modulate cell contact persistence

What is Flamingo? Usui et al. Cell. (1999)Veeman et al. Dev Cell. (2003) Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled. Wnt11 and Fmi control convergent extension movements during zebrafish gastrulation. Formstone et al. Dev Biol. (2005) Seifert et al. Nat Rev Genet. (2007)

Fmi2 colocalizes with Fz7 and Wnt11 at cell contacts and increases persistence Fmi2 is able to induce accumulation of itself and Fz7 independently of Wnt11

Fmi2 colocalizes with Fz7 and Wnt11 at cell contacts and increases persistence Fmi MO : Fmi morppholinos targeted against fmi1a, fmi1b, fmi2

Endogenous subcellular sites of Wnt11 and Fz7 activity marked by Dsh-YFP recruitment to the plasma membrane Slb mutant : inactive C-terminal truncated wnt11

Endogenous subcellular sites of Wnt11 and Fz7 activity marked by Dsh-YFP recruitment to the plasma membrane Fm464 : plasma membrane marker

Wnt11 persist at cell contacts and is required for contact persistence Wnt11-YFP + GPI-anchored RFP

Wnt11 persist at cell contacts and is required for contact persistence

Summary Wnt11 Dsh Enhance cell adhesion Fz7 accumulation Dsh accumulation Fmi colocalizes with Fz7 PCP pathway