title: β-Catenin signaling regulates the timing of cell differentiation in mouse retinal progenitor cells.
abstract: Wnt signaling is important in development and carcinogenesis. We previously showed that active β-catenin or Lef-1 in the mammalian retinal culture prevents differentiation of retinal cells without modifying cellular proliferation. In this study, we investigated the in vivo role of β-catenin in mouse retinal differentiation in transgenic mice, in which retinal-specific activation or inactivation of β-catenin was achieved with Cre recombinase. The gain-of-function mice exhibited small eyes and large cell aggregates consisting of early progenitor cells labeled with SSEA-1 in the peripheral retina. In the loss-of-function mice, we observed a reduced number of SSEA-1-positive progenitor cells and the presence of differentiated cells in the β-catenin ablated retinal region. Interestingly, the number of proliferating cells in the β-catenin gain-of-function mice was highly downregulated, and the proliferation index detected by Ki67 expression was slightly lower than that of control mice in the β-catenin loss-of-function mice. The Gsk-3β inhibitor BIO induced expression of Id3, which was highly expressed in SSEA-1-positive cells, and transiently maintained SSEA-1-positive retinal progenitor cells (RPCs). Forced expression of Id3 in RPCs mimicked the effects of BIO. Taken together, β-catenin signaling regulates the timing of differentiation in RPCs by inhibiting premature differentiation of them partly through the regulation of Id3 expression.
authors.affiliation: Department of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 108-8639 Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ouchi
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Baba
authors.forename: Hideto
authors.initials: H
authors.lastname: Koso
authors.forename: Makoto M
authors.initials: MM
authors.lastname: Taketo
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Sumiko
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics / Q000378:metabolism; D016256:Lewis X Antigen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D012160:Retina / Q000166:cytology* / Q000473:pathology / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D051796:Inhibitor of Differentiation Proteins; D016256:Lewis X Antigen; D051153:Wnt Proteins; D051176:beta Catenin; C067679:Idb3 protein, mouse