Reciprocal expression of lin ‐ 41 and the microRNAs let ‐ 7 and mir ‐ 125 during mouse embryogenesis

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. Developmental Dynamics 234:1046–1054, 2005. © 2005 Wiley‐Liss, Inc.