witzel et al. j cell biol. (2006) wnt11 controls cell contact persistence by local accumulation of...

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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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Page 1: Witzel et al. J Cell Biol. (2006) Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane

Witzel et al. J Cell Biol. (2006)

Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane

Page 2: 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.

Page 3: Witzel et al. J Cell Biol. (2006) Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane

Gastrulation movements in zebrafish

Solnica-Krezel L. Curr Opin Genet Dev. (2006)

Page 4: Witzel et al. J Cell Biol. (2006) Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane

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)

Page 5: Witzel et al. J Cell Biol. (2006) Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane

Wnt11 induces local accumulation of Fz7 at the plasma membrane

5pg mRNA 10pg mRNA 20pg mRNA

Lyn : membrane-bound kinase - membrane marker

Page 6: Witzel et al. J Cell Biol. (2006) Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane

Wnt11 locally accumulates with Fz7 at the plasma membrane

Wnt11 producing cell

Wnt11 receiving cell

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

Wnt11-induced Fz7 accumulations form on contacting plasma membranes

Wnt11 induces the accumulation of Fz7 on both cells.

Fz7-YFP and Fz7-CFPaccumulation

Page 8: Witzel et al. J Cell Biol. (2006) Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane

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.

Page 9: Witzel et al. J Cell Biol. (2006) Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane

Wnt11-induced accumulations of Fz7 modulate cell contact persistence

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

Page 10: Witzel et al. J Cell Biol. (2006) Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane

Wnt11-induced accumulations of Fz7 modulate cell contact persistence

Page 11: Witzel et al. J Cell Biol. (2006) Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane

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)

Page 12: Witzel et al. J Cell Biol. (2006) Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane

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

Page 13: Witzel et al. J Cell Biol. (2006) Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane

Fmi2 colocalizes with Fz7 and Wnt11 at cell contacts and increases persistence

Fmi MO : Fmi morppholinos targeted against fmi1a, fmi1b, fmi2

Page 14: Witzel et al. J Cell Biol. (2006) Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane

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

Slb mutant : inactive C-terminal truncated wnt11

Page 15: Witzel et al. J Cell Biol. (2006) Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane

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

Fm464 : plasma membrane marker

Page 16: Witzel et al. J Cell Biol. (2006) Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane

Wnt11 persist at cell contacts and is required for contact persistence

Wnt11-YFP + GPI-anchored RFP

Page 17: Witzel et al. J Cell Biol. (2006) Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane

Wnt11 persist at cell contacts and is required for contact persistence

Page 18: Witzel et al. J Cell Biol. (2006) Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane

Summary

Wnt11

Dsh Dsh Dsh

Dsh

Enhance cell adhesion

Fz7 accumulation

Dsh accumulation

Fmi colocalizes with Fz7

PCP pathway