• limb development;
  • heterochronic gene;
  • developmental timing;
  • pattern formation;
  • lin-41;
  • let-7;
  • miR-125;
  • miRNA;
  • muscle development;
  • vascular development;
  • Sonic Hedgehog;
  • Shh;
  • Fgf


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. Developmental Dynamics 234:948–960, 2005. © 2005 Wiley-Liss, Inc.