Wnt signaling mediates self-organization and axis formation in embryoid bodies.
Embryonic stem cells (ESCs) form descendants of all three germ layers when differentiated as aggregates, termed embryoid bodies. In vivo, differentiation of cells depends on signals and morphogen gradients that provide instructive and positional cues, but do such gradients exist in embryoid bodies? We report here the establishment of anteroposterior polarity and the formation of a primitive streak-like region in the embryoid body, dependent on local activation of the Wnt pathway. In this region, cells undergo an epithelial-to-mesenchymal transition and differentiate into mesendodermal progenitors. Exogenous Wnt3a protein posteriorizes the embryoid body, resulting in predominantly mesendodermal differentiation. Conversely, inhibiting Wnt signaling promotes anterior character and results in neurectodermal differentiation. The activation of Wnt signaling and primitive streak formation requires external signals but is self-reinforcing after initiation. Our findings show that the Wnt pathway mediates the local execution of a gastrulation-like process in the embryoid body, which displays an unexpected degree of self-organization.
ten Berge
Derk
D
Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. derk@stanford.edu
Koole
Wouter
W
Fuerer
Christophe
C
Fish
Matt
M
Eroglu
Elif
E
Nusse
Roel
R
D000818:Animals; D060466:Axin Protein; D019521:Body Patterning; D002454:Cell Differentiation; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics; D047108:Embryonic Development / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology*; D006706:Homeostasis; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D054258:Neural Plate / Q000166:cytology / Q000378:metabolism*; D054240:Primitive Streak / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D051153:Wnt Proteins / Q000378:metabolism*; D060508:Wnt3 Protein; D060509:Wnt3A Protein
D060466:Axin Protein; C111729:Axin2 protein, mouse; D003598:Cytoskeletal Proteins; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse