RRC ID 60013
Author Turner KJ, Hoyle J, Valdivia LE, Cerveny KL, Hart W, Mangoli M, Geisler R, Rees M, Houart C, Poole RJ, Wilson SW, Gestri G.
Title Abrogation of Stem Loop Binding Protein (Slbp) function leads to a failure of cells to transition from proliferation to differentiation, retinal coloboma and midline axon guidance deficits.
Journal PLoS One
Abstract Through forward genetic screening for mutations affecting visual system development, we identified prominent coloboma and cell-autonomous retinal neuron differentiation, lamination and retinal axon projection defects in eisspalte (ele) mutant zebrafish. Additional axonal deficits were present, most notably at midline axon commissures. Genetic mapping and cloning of the ele mutation showed that the affected gene is slbp, which encodes a conserved RNA stem-loop binding protein involved in replication dependent histone mRNA metabolism. Cells throughout the central nervous system remained in the cell cycle in ele mutant embryos at stages when, and locations where, post-mitotic cells have differentiated in wild-type siblings. Indeed, RNAseq analysis showed down-regulation of many genes associated with neuronal differentiation. This was coincident with changes in the levels and spatial localisation of expression of various genes implicated, for instance, in axon guidance, that likely underlie specific ele phenotypes. These results suggest that many of the cell and tissue specific phenotypes in ele mutant embryos are secondary to altered expression of modules of developmental regulatory genes that characterise, or promote transitions in, cell state and require the correct function of Slbp-dependent histone and chromatin regulatory genes.
Volume 14(1)
Pages e0211073
Published 2019-1-1
DOI 10.1371/journal.pone.0211073
PII PONE-D-19-00337
PMID 30695021
PMC PMC6350959
MeSH Animals Animals, Genetically Modified* / embryology Animals, Genetically Modified* / genetics Axon Guidance / genetics* Cell Differentiation* Cell Proliferation* Coloboma* / embryology Coloboma* / genetics Coloboma* / pathology Histones / genetics Histones / metabolism RNA, Messenger / biosynthesis RNA, Messenger / genetics Retinal Diseases* / embryology Retinal Diseases* / genetics Retinal Diseases* / pathology Zebrafish* / embryology Zebrafish* / genetics Zebrafish Proteins / deficiency*
IF 2.776
Times Cited 3
Zebrafish Tg(EF1α:mAG-zGem(1/100))rw0410h Tg(EF1α:mKO2-zCdt1(1/190))rw0405b