| Whole-genome microRNA screening identifies let-7 and mir-18 as regulators of germ layer formation during early embryogenesis. | |
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MedLine Citation:
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PMID: 23152446 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Tight control over the segregation of endoderm, mesoderm, and ectoderm is essential for normal embryonic development of all species, yet how neighboring embryonic blastomeres can contribute to different germ layers has never been fully explained. We postulated that microRNAs, which fine-tune many biological processes, might modulate the response of embryonic blastomeres to growth factors and other signals that govern germ layer fate. A systematic screen of a whole-genome microRNA library revealed that the let-7 and miR-18 families increase mesoderm at the expense of endoderm in mouse embryonic stem cells. Both families are expressed in ectoderm and mesoderm, but not endoderm, as these tissues become distinct during mouse and frog embryogenesis. Blocking let-7 function in vivo dramatically affected cell fate, diverting presumptive mesoderm and ectoderm into endoderm. siRNA knockdown of computationally predicted targets followed by mutational analyses revealed that let-7 and miR-18 down-regulate Acvr1b and Smad2, respectively, to attenuate Nodal responsiveness and bias blastomeres to ectoderm and mesoderm fates. These findings suggest a crucial role for the let-7 and miR-18 families in germ layer specification and reveal a remarkable conservation of function from amphibians to mammals. |
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Authors:
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Alexandre R Colas; Wesley L McKeithan; Thomas J Cunningham; Paul J Bushway; Lana X Garmire; Gregg Duester; Shankar Subramaniam; Mark Mercola |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-11-14 |
Journal Detail:
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Title: Genes & development Volume: 26 ISSN: 1549-5477 ISO Abbreviation: Genes Dev. Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-04 Completed Date: 2013-01-25 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 8711660 Medline TA: Genes Dev Country: United States |
Other Details:
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Languages: eng Pagination: 2567-79 Citation Subset: IM |
Affiliation:
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Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cells, Cultured DNA Mutational Analysis Embryonic Development / genetics* Embryonic Stem Cells Gene Expression Regulation, Developmental* Gene Knockdown Techniques Genome / genetics* Germ Layers / embryology* Mice MicroRNAs / genetics, metabolism* Xenopus laevis |
| Grant Support | |
ID/Acronym/Agency:
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P30 CA030199-30/CA/NCI NIH HHS; R01 HL113601/HL/NHLBI NIH HHS; R01 HL113601/HL/NHLBI NIH HHS; R33 HL087375/HL/NHLBI NIH HHS; R33 HL088266/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/MIRN18 microRNA, mouse; 0/MicroRNAs; 0/mirnlet7 microRNA, mouse |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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