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

Dev Dyn. 2005 Dec;234(4):1046-54. doi: 10.1002/dvdy.20599.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Pairing
  • Base Sequence
  • Binding Sites / genetics
  • Blotting, Northern
  • Cloning, Molecular
  • Conserved Sequence / genetics
  • DNA Primers
  • Embryo, Mammalian / metabolism*
  • Extremities / embryology
  • Gene Components
  • Gene Expression Regulation, Developmental*
  • In Situ Hybridization
  • Mice
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Sequence Analysis, DNA
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • DNA Primers
  • LIN-41 protein, mouse
  • MicroRNAs
  • Transcription Factors