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miR-302 Is Required for Timing of Neural Differentiation, Neural Tube Closure, and Embryonic Viability
The evolutionarily conserved miR-302 family of microRNAs is expressed during early mammalian embryonic development. Here, we report that deletion of miR-302a-d in mice results in a fully penetrant late embryonic lethal phenotype. Knockout embryos have an anterior neural tube closure defect associate...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741278/ https://www.ncbi.nlm.nih.gov/pubmed/26212322 http://dx.doi.org/10.1016/j.celrep.2015.06.074 |
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author | Parchem, Ronald J. Moore, Nicole Fish, Jennifer L. Parchem, Jacqueline G. Braga, Tarcio T. Shenoy, Archana Oldham, Michael C. Rubenstein, John L.R. Schneider, Richard A. Blelloch, Robert |
author_facet | Parchem, Ronald J. Moore, Nicole Fish, Jennifer L. Parchem, Jacqueline G. Braga, Tarcio T. Shenoy, Archana Oldham, Michael C. Rubenstein, John L.R. Schneider, Richard A. Blelloch, Robert |
author_sort | Parchem, Ronald J. |
collection | PubMed |
description | The evolutionarily conserved miR-302 family of microRNAs is expressed during early mammalian embryonic development. Here, we report that deletion of miR-302a-d in mice results in a fully penetrant late embryonic lethal phenotype. Knockout embryos have an anterior neural tube closure defect associated with a thickened neuroepithelium. The neuroepithelium shows increased progenitor proliferation, decreased cell death, and precocious neuronal differentiation. mRNA profiling at multiple time points during neurulation uncovers a complex pattern of changing targets over time. Overexpression of one of these targets, Fgf15, in the neuroepithelium of the chick embryo induces precocious neuronal differentiation. Compound mutants between mir-302 and the related mir-290 locus have a synthetic lethal phenotype prior to neurulation. Our results show that mir-302 helps regulate neurulation by suppressing neural progenitor expansion and precocious differentiation. Furthermore, these results uncover redundant roles for mir-290 and mir-302 early in development. |
format | Online Article Text |
id | pubmed-4741278 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-47412782016-02-04 miR-302 Is Required for Timing of Neural Differentiation, Neural Tube Closure, and Embryonic Viability Parchem, Ronald J. Moore, Nicole Fish, Jennifer L. Parchem, Jacqueline G. Braga, Tarcio T. Shenoy, Archana Oldham, Michael C. Rubenstein, John L.R. Schneider, Richard A. Blelloch, Robert Cell Rep Article The evolutionarily conserved miR-302 family of microRNAs is expressed during early mammalian embryonic development. Here, we report that deletion of miR-302a-d in mice results in a fully penetrant late embryonic lethal phenotype. Knockout embryos have an anterior neural tube closure defect associated with a thickened neuroepithelium. The neuroepithelium shows increased progenitor proliferation, decreased cell death, and precocious neuronal differentiation. mRNA profiling at multiple time points during neurulation uncovers a complex pattern of changing targets over time. Overexpression of one of these targets, Fgf15, in the neuroepithelium of the chick embryo induces precocious neuronal differentiation. Compound mutants between mir-302 and the related mir-290 locus have a synthetic lethal phenotype prior to neurulation. Our results show that mir-302 helps regulate neurulation by suppressing neural progenitor expansion and precocious differentiation. Furthermore, these results uncover redundant roles for mir-290 and mir-302 early in development. 2015-07-23 2015-08-04 /pmc/articles/PMC4741278/ /pubmed/26212322 http://dx.doi.org/10.1016/j.celrep.2015.06.074 Text en http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Parchem, Ronald J. Moore, Nicole Fish, Jennifer L. Parchem, Jacqueline G. Braga, Tarcio T. Shenoy, Archana Oldham, Michael C. Rubenstein, John L.R. Schneider, Richard A. Blelloch, Robert miR-302 Is Required for Timing of Neural Differentiation, Neural Tube Closure, and Embryonic Viability |
title | miR-302 Is Required for Timing of Neural Differentiation, Neural Tube Closure, and Embryonic Viability |
title_full | miR-302 Is Required for Timing of Neural Differentiation, Neural Tube Closure, and Embryonic Viability |
title_fullStr | miR-302 Is Required for Timing of Neural Differentiation, Neural Tube Closure, and Embryonic Viability |
title_full_unstemmed | miR-302 Is Required for Timing of Neural Differentiation, Neural Tube Closure, and Embryonic Viability |
title_short | miR-302 Is Required for Timing of Neural Differentiation, Neural Tube Closure, and Embryonic Viability |
title_sort | mir-302 is required for timing of neural differentiation, neural tube closure, and embryonic viability |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741278/ https://www.ncbi.nlm.nih.gov/pubmed/26212322 http://dx.doi.org/10.1016/j.celrep.2015.06.074 |
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