title: Analysis of the regulation of lin-41 during chick and mouse limb development.
abstract: 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.
authors.affiliation: Department of Anatomy, University of Wisconsin, Madison, 53706, USA.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Lancman
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Caruccio
authors.forename: Brian D
authors.initials: BD
authors.lastname: Harfe
authors.forename: Amy E
authors.initials: AE
authors.lastname: Pasquinelli
authors.forename: Jeoffrey J
authors.initials: JJ
authors.lastname: Schageman
authors.forename: Alexander
authors.initials: A
authors.lastname: Pertsemlidis
authors.forename: John F
authors.initials: JF
authors.lastname: Fallon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015152:Blotting, Northern; D002642:Chick Embryo; D003001:Cloning, Molecular; D019295:Computational Biology; D005121:Extremities / Q000196:embryology*; D040461:Gene Components; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D051379:Mice; D008817:Mice, Mutant Strains; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008863:Microspheres; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000235:genetics; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: C511366:LIN-41 protein, mouse; D035683:MicroRNAs; D014157:Transcription Factors