Wnt11 functions in gastrulation by controlling cell cohesion through Rab5c and E-cadherin.
Wnt11 plays a central role in tissue morphogenesis during vertebrate gastrulation, but the molecular and cellular mechanisms by which Wnt11 exerts its effects remain poorly understood. Here, we show that Wnt11 functions during zebrafish gastrulation by regulating the cohesion of mesodermal and endodermal (mesendodermal) progenitor cells. Importantly, we demonstrate that Wnt11 activity in this process is mediated by the GTPase Rab5, a key regulator of early endocytosis, as blocking Rab5c activity in wild-type embryos phenocopies slb/wnt11 mutants, and enhancing Rab5c activity in slb/wnt11 mutant embryos rescues the mutant phenotype. In addition, we find that Wnt11 and Rab5c control the endocytosis of E-cadherin and are required in mesendodermal cells for E-cadherin-mediated cell cohesion. Together, our results suggest that Wnt11 controls tissue morphogenesis by modulating E-cadherin-mediated cell cohesion through Rab5c, a novel mechanism of Wnt signaling in gastrulation.
Ulrich
Florian
F
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Krieg
Michael
M
Schötz
Eva-Maria
EM
Link
Vinzenz
V
Castanon
Irinka
I
Schnabel
Viktor
V
Taubenberger
Anna
A
Mueller
Daniel
D
Puech
Pierre-Henri
PH
Heisenberg
Carl-Philipp
CP
D000818:Animals; D030801:Animals, Genetically Modified; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement / Q000502:physiology; D004705:Endocytosis / Q000502:physiology; D005775:Gastrula / Q000166:cytology / Q000502:physiology*; D009024:Morphogenesis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D015820:Cadherins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D051153:Wnt Proteins; C092568:Wnt11 protein, zebrafish; D029961:Zebrafish Proteins; C505379:Rab5c protein, zebrafish; D020696:rab5 GTP-Binding Proteins