title: Stem-loop binding protein is required for retinal cell proliferation, neurogenesis, and intraretinal axon pathfinding in zebrafish.
abstract: 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.
authors.affiliation: Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna, Okinawa 904-0495, Japan.
authors.forename: Fumiyasu
authors.initials: F
authors.lastname: Imai
authors.affiliation: Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna, Okinawa 904-0495, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Yoshizawa
authors.affiliation: Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna, Okinawa 904-0495, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Matsuzaki
authors.affiliation: Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna, Okinawa 904-0495, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Oguri
authors.affiliation: Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna, Okinawa 904-0495, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Araragi
authors.affiliation: Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna, Okinawa 904-0495, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nishiwaki
authors.affiliation: Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna, Okinawa 904-0495, Japan. Electronic address: masai@oist.jp.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Masai
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000096:biosynthesis; D049452:Green Fluorescent Proteins; D006657:Histones / Q000235:genetics; D009154:Mutation; D055495:Neurogenesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D051880:Receptors, Notch / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000196:embryology*; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D054377:Chemokine CXCL12; D006657:Histones; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D051880:Receptors, Notch; C584140:SLBP protein, zebrafish; D029961:Zebrafish Proteins; C579453:cxcl12a protein, zebrafish; D049452:Green Fluorescent Proteins; D044767:Ubiquitin-Protein Ligases; C471932:mib1 protein, zebrafish
keywords: Neurogenesis; Notch; Proliferation; Retina; Stem-loop binding protein; Zebrafish