ZFIN ID: ZDB-PUB-140812-8
Stem-loop binding protein is required for retinal cell proliferation, neurogenesis, and intraretinal axon pathfinding in zebrafish
Imai, F., Yoshizawa, A., Matsuzaki, A., Oguri, E., Araragi, M., Nishiwaki, Y., Masai, I.
Date: 2014
Source: Developmental Biology   394(1): 94-109 (Journal)
Registered Authors: Araragi, Masato, Imai, Fumiyasu, Masai, Ichiro, Nishiwaki, Yuko, Oguri, Eri
Keywords: Neurogenesis, Notch, Proliferation, Retina, Stem-loop binding protein, Zebrafish
MeSH Terms:
  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Chemokine CXCL12/biosynthesis
  • Green Fluorescent Proteins
  • Histones/genetics
  • Mutation
  • Neurogenesis
  • RNA, Messenger/biosynthesis
  • RNA, Messenger/genetics
  • RNA-Binding Proteins/biosynthesis*
  • RNA-Binding Proteins/genetics
  • Receptors, Notch/metabolism*
  • Retina/cytology
  • Retina/embryology*
  • Signal Transduction/genetics
  • Stem Cells
  • Ubiquitin-Protein Ligases/genetics
  • Zebrafish/embryology*
  • Zebrafish Proteins/biosynthesis
  • Zebrafish Proteins/genetics
PubMed: 25106852 Full text @ Dev. Biol.
In the developing retina, neurogenesis and cell differentiation are coupled with cell proliferation. However, molecular mechanisms that coordinate cell proliferation and differentiation are not fully understood. In this study, we found that retinal neurogenesis is severely delayed in the zebrafish stem-loop binding protein (slbp) mutant. SLBP binds to a stem-loop structure at the 3'-end of histone mRNAs, and regulates a replication-dependent synthesis and degradation of histone proteins. Retinal cell proliferation becomes slower in the slbp1 mutant, resulting in cessation of retinal stem cell proliferation. Although retinal stem cells cease proliferation by 2 days postfertilization (dpf) in the slbp mutant, retinal progenitor cells in the central retina continue to proliferate and generate neurons until at least 5dpf. We found that this progenitor proliferation depends on Notch signaling, suggesting that Notch signaling maintains retinal progenitor proliferation when faced with reduced SLBP activity. Thus, SLBP is required for retinal stem cell maintenance. SLBP and Notch signaling are required for retinal progenitor cell proliferation and subsequent neurogenesis. We also show that SLBP1 is required for intraretinal axon pathfinding, probably through morphogenesis of the optic stalk, which expresses attractant cues. Taken together, these data indicate important roles of SLBP in retinal development.