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β-Catenin signaling regulates the timing of cell differentiation in mouse retinal progenitor cells
- Source :
- Molecular and cellular neurosciences. 46(4)
- Publication Year :
- 2010
-
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.
- Subjects :
- Genetically modified mouse
Beta-catenin
Proliferation index
Cellular differentiation
Lewis X Antigen
Retina
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Mice
medicine
Animals
Progenitor cell
Promoter Regions, Genetic
Molecular Biology
Cells, Cultured
beta Catenin
biology
Stem Cells
Wnt signaling pathway
Retinal
Cell Differentiation
Cell Biology
Molecular biology
Mice, Inbred C57BL
Wnt Proteins
medicine.anatomical_structure
chemistry
biology.protein
Inhibitor of Differentiation Proteins
Biomarkers
Signal Transduction
Subjects
Details
- ISSN :
- 10959327
- Volume :
- 46
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Molecular and cellular neurosciences
- Accession number :
- edsair.doi.dedup.....fe7a798bf7ace86615fc30effdcdc6b7