Document Detail


Whole-genome microRNA screening identifies let-7 and mir-18 as regulators of germ layer formation during early embryogenesis.
MedLine Citation:
PMID:  23152446     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Alexandre R Colas; Wesley L McKeithan; Thomas J Cunningham; Paul J Bushway; Lana X Garmire; Gregg Duester; Shankar Subramaniam; Mark Mercola
Related Documents :
18773496 - Left-asymmetric expression of galanin in the linear heart tube of the mouse embryo is i...
18515646 - Regulation of kv4 channel expression in failing rat heart by the thioredoxin system.
23446346 - Natural rna circles function as efficient microrna sponges.
16376326 - Alterations of the preproenkephalin system in cardiac hypertrophy and its role in atrio...
25426416 - Mycn promotes trpm7 expression and cell migration in neuroblastoma through a process th...
11369616 - Epidermal growth factor-like ligands and erbb genes in the peri-implantation rabbit ute...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-14
Journal Detail:
Title:  Genes & development     Volume:  26     ISSN:  1549-5477     ISO Abbreviation:  Genes Dev.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-04     Completed Date:  2013-01-25     Revised Date:  2014-04-16    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2567-79     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
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:
P30 CA030199/CA/NCI NIH HHS; P30 CA030199-30/CA/NCI NIH HHS; R01 GM062848/GM/NIGMS 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:
0/MIRN18 microRNA, mouse; 0/MicroRNAs; 0/mirnlet7 microRNA, mouse
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Retroaortic abscess: an unusual complication of a retained epicardial pacing wire.
Next Document:  The role of PR-Set7 in replication licensing depends on Suv4-20h.