A directional Wnt/beta-catenin-Sox2-proneural pathway regulates the transition from proliferation to differentiation in the Xenopus retina.
Progenitor cells in the central nervous system must leave the cell cycle to become neurons and glia, but the signals that coordinate this transition remain largely unknown. We previously found that Wnt signaling, acting through Sox2, promotes neural competence in the Xenopus retina by activating proneural gene expression. We now report that Wnt and Sox2 inhibit neural differentiation through Notch activation. Independently of Sox2, Wnt stimulates retinal progenitor proliferation and this, when combined with the block on differentiation, maintains retinal progenitor fates. Feedback inhibition by Sox2 on Wnt signaling and by the proneural transcription factors on Sox2 mean that each element of the core pathway activates the next element and inhibits the previous one, providing a directional network that ensures retinal cells make the transition from progenitors to neurons and glia.
Agathocleous
Michalis
M
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Iordanova
Ilina
I
Willardsen
Minde I
MI
Xue
Xiao Yan
XY
Vetter
Monica L
ML
Harris
William A
WA
Moore
Kathryn B
KB
D000818:Animals; D030801:Animals, Genetically Modified; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D008954:Models, Biological; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D051880:Receptors, Notch / Q000235:genetics / Q000502:physiology; D012160:Retina / Q000196:embryology* / Q000502:physiology*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology*; D029867:Xenopus Proteins / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000502:physiology*
C495266:CTNNB1 protein, Xenopus; D051880:Receptors, Notch; D055748:SOXB1 Transcription Factors; D051153:Wnt Proteins; D029867:Xenopus Proteins; D051176:beta Catenin; C527781:sox2 protein, Xenopus