期刊
DEVELOPMENTAL DYNAMICS
卷 234, 期 4, 页码 1046-1054出版社
WILEY
DOI: 10.1002/dvdy.20599
关键词
microRNAs; lin-41; let-7; mir-125; developmental timing; mouse embryogenesis; expression pattern; limb development; heterochronic gene
资金
- NIGMS NIH HHS [1R01GM64701, F32GM071157, R01 GM064701-04, F32 GM071157, R01 GM064701] Funding Source: Medline
In C. elegans, heterochronic genes control the timing of cell fate determination during development. Two heterochronic genes, let-7 and lin-4, encode microRNAs (miRNAs) that down-regulate a third heterochronic gene lin-41 by binding to complementary sites in its 3'UTR. let-7 and lin-4 are conserved in mammals. Here we report the cloning and sequencing of mammalian lin-41 orthologs. We find that mouse and human lin-41 genes contain predicted conserved complementary sites for let-7 and the lin-4 ortholog, mir-125, in their 3'UTRs. Mouse lin-41 (Mlin-41) is temporally expressed in developing mouse embryos, most dramatically in the limb buds. Mlin-41 is down-regulated during mid-embryogenesis at the time when mouse let-7c and mir-125 RNA levels are up-regulated. Our results suggest that mammalian lin-41 is temporally regulated by miRNAs in order to direct key developmental events such as limb formation.
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