RRC ID 403
Author Yamaguchi M, Tonou-Fujimori N, Komori A, Maeda R, Nojima Y, Li H, Okamoto H, Masai I.
Title Histone deacetylase 1 regulates retinal neurogenesis in zebrafish by suppressing Wnt and Notch signaling pathways.
Journal Development
Abstract In the developing vertebrate retina, progenitor cells initially proliferate but begin to produce postmitotic neurons when neuronal differentiation occurs. However, the mechanism that determines whether retinal progenitor cells continue to proliferate or exit from the cell cycle and differentiate is largely unknown. Here, we report that histone deacetylase 1 (Hdac1) is required for the switch from proliferation to differentiation in the zebrafish retina. We isolated a zebrafish mutant, ascending and descending (add), in which retinal cells fail to differentiate into neurons and glial cells but instead continue to proliferate. The cloning of the add gene revealed that it encodes Hdac1. Furthermore, the ratio of the number of differentiating cells to that of proliferating cells increases in proportion to Hdac activity, suggesting that Hdac proteins regulate a crucial step of retinal neurogenesis in zebrafish. Canonical Wnt signaling promotes the proliferation of retinal cells in zebrafish, and Notch signaling inhibits neuronal differentiation through the activation of a neurogenic inhibitor, Hairy/Enhancer-of-split (Hes). We found that both the Wnt and Notch/Hes pathways are activated in the add mutant retina. The cell-cycle progression and the upregulation of Hes expression in the add mutant retina can be inhibited by the blockade of Wnt and Notch signaling, respectively. These data suggest that Hdac1 antagonizes these pathways to promote cell-cycle exit and the subsequent neurogenesis in zebrafish retina. Taken together, these data suggest that Hdac1 functions as a dual switch that suppresses both cell-cycle progression and inhibition of neurogenesis in the zebrafish retina.
Volume 132(13)
Pages 3027-43
Published 2005-7
DOI 10.1242/dev.01881
PII 132/13/3027
PMID 15944187
MeSH Amino Acid Sequence Animals Cell Cycle / genetics Cell Cycle Proteins / metabolism Cell Differentiation / physiology Cell Proliferation Cyclin D1 / metabolism Cyclin-Dependent Kinase Inhibitor p27 Down-Regulation / genetics Down-Regulation / physiology* Growth Inhibitors / genetics Growth Inhibitors / physiology Histone Deacetylase 1 Histone Deacetylases / genetics Histone Deacetylases / metabolism* Intercellular Signaling Peptides and Proteins / metabolism* Membrane Proteins / antagonists & inhibitors Membrane Proteins / metabolism* Molecular Sequence Data Mutation Receptors, Notch Retina / cytology Retina / embryology* Signal Transduction / genetics* Tumor Suppressor Proteins / metabolism Wnt Proteins Zebrafish / embryology* Zebrafish / genetics Zebrafish Proteins / genetics Zebrafish Proteins / metabolism*
IF 5.413
Times Cited 132
Zebrafish rw021(Tg(ath5:GFP)) ? rw399? RIKEN WT (RW)