Analysis of the regulation of lin-41 during chick and mouse limb development

Dev Dyn. 2005 Dec;234(4):948-60. doi: 10.1002/dvdy.20591.


We have cloned the chicken and mouse orthologues of the Caenorhabditis elegans heterochronic gene lin-41. During limb development, lin-41 is expressed in three phases over developmental time and most notably is associated with the developing autopod. Using chicken and mouse mutants and bead implantations, we report that lin-41 is genetically and biochemically downstream of both the Shh and Fgf signaling pathways. In C. elegans, it is proposed that lin-41 activity is temporally regulated by miRNAs (let-7 and lin-4) that bind to complementary sites in the lin-41 3'-untranslated region (UTR). Taking a bioinformatics approach, we also report the presence of potential miRNA binding sites in the 3'-UTR of chicken lin-41, including sites for the chicken orthologues of both C. elegans let-7 and lin-4. Finally, we show that these miRNAs and others are expressed in the chick limb consistent with the hypothesis that they regulate chicken Lin-41 activity in vivo.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites / genetics
  • Blotting, Northern
  • Chick Embryo
  • Cloning, Molecular
  • Computational Biology
  • Extremities / embryology*
  • Gene Components
  • Gene Expression Regulation, Developmental*
  • In Situ Hybridization
  • Mice
  • Mice, Mutant Strains
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Microspheres
  • Molecular Sequence Data
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Signal Transduction / genetics
  • Species Specificity
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*


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