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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2015-08-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715007123 |
| _version_ | 1819260618659594240 |
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| author | Ronald J. Parchem Nicole Moore Jennifer L. Fish Jacqueline G. Parchem Tarcio T. Braga Archana Shenoy Michael C. Oldham John L.R. Rubenstein Richard A. Schneider Robert Blelloch |
| author_facet | Ronald J. Parchem Nicole Moore Jennifer L. Fish Jacqueline G. Parchem Tarcio T. Braga Archana Shenoy Michael C. Oldham John L.R. Rubenstein Richard A. Schneider Robert Blelloch |
| author_sort | Ronald J. Parchem |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-23T19:28:46Z |
| format | Article |
| id | doaj.art-e6b84f7b9cab47a4bbf646392a2d115f |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-23T19:28:46Z |
| publishDate | 2015-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-e6b84f7b9cab47a4bbf646392a2d115f2022-12-21T17:33:59ZengElsevierCell Reports2211-12472015-08-0112576077310.1016/j.celrep.2015.06.074miR-302 Is Required for Timing of Neural Differentiation, Neural Tube Closure, and Embryonic ViabilityRonald J. Parchem0Nicole Moore1Jennifer L. Fish2Jacqueline G. Parchem3Tarcio T. Braga4Archana Shenoy5Michael C. Oldham6John L.R. Rubenstein7Richard A. Schneider8Robert Blelloch9The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USAThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USADepartment of Orthopaedic Surgery, University of California, San Francisco, San Francisco, CA 94143, USADepartment of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USAThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USAThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USAThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USADepartment of Psychiatry, University of California, San Francisco, San Francisco, CA 94143, USADepartment of Orthopaedic Surgery, University of California, San Francisco, San Francisco, CA 94143, USAThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USAThe 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.http://www.sciencedirect.com/science/article/pii/S2211124715007123 |
| spellingShingle | Ronald J. Parchem Nicole Moore Jennifer L. Fish Jacqueline G. Parchem Tarcio T. Braga Archana Shenoy Michael C. Oldham John L.R. Rubenstein Richard A. Schneider Robert Blelloch miR-302 Is Required for Timing of Neural Differentiation, Neural Tube Closure, and Embryonic Viability Cell Reports |
| 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 |
| url | http://www.sciencedirect.com/science/article/pii/S2211124715007123 |
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