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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

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...

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Autores principales: Turner, Katherine J., Hoyle, Jacqueline, Valdivia, Leonardo E., Cerveny, Kara L., Hart, Wendy, Mangoli, Maryam, Geisler, Robert, Rees, Michele, Houart, Corinne, Poole, Richard J., Wilson, Stephen W., Gestri, Gaia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350959/
https://www.ncbi.nlm.nih.gov/pubmed/30695021
http://dx.doi.org/10.1371/journal.pone.0211073
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author Turner, Katherine J.
Hoyle, Jacqueline
Valdivia, Leonardo E.
Cerveny, Kara L.
Hart, Wendy
Mangoli, Maryam
Geisler, Robert
Rees, Michele
Houart, Corinne
Poole, Richard J.
Wilson, Stephen W.
Gestri, Gaia
author_facet Turner, Katherine J.
Hoyle, Jacqueline
Valdivia, Leonardo E.
Cerveny, Kara L.
Hart, Wendy
Mangoli, Maryam
Geisler, Robert
Rees, Michele
Houart, Corinne
Poole, Richard J.
Wilson, Stephen W.
Gestri, Gaia
author_sort Turner, Katherine J.
collection PubMed
description 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.
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spelling pubmed-63509592019-02-15 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 Turner, Katherine J. Hoyle, Jacqueline Valdivia, Leonardo E. Cerveny, Kara L. Hart, Wendy Mangoli, Maryam Geisler, Robert Rees, Michele Houart, Corinne Poole, Richard J. Wilson, Stephen W. Gestri, Gaia PLoS One Research Article 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. Public Library of Science 2019-01-29 /pmc/articles/PMC6350959/ /pubmed/30695021 http://dx.doi.org/10.1371/journal.pone.0211073 Text en © 2019 Turner et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Turner, Katherine J.
Hoyle, Jacqueline
Valdivia, Leonardo E.
Cerveny, Kara L.
Hart, Wendy
Mangoli, Maryam
Geisler, Robert
Rees, Michele
Houart, Corinne
Poole, Richard J.
Wilson, Stephen W.
Gestri, Gaia
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
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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350959/
https://www.ncbi.nlm.nih.gov/pubmed/30695021
http://dx.doi.org/10.1371/journal.pone.0211073
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