title: The miR-30 microRNA family targets smoothened to regulate hedgehog signalling in zebrafish early muscle development.
abstract: The importance of microRNAs in development is now widely accepted. However, identifying the specific targets of individual microRNAs and understanding their biological significance remains a major challenge. We have used the zebrafish model system to evaluate the expression and function of microRNAs potentially involved in muscle development and study their interaction with predicted target genes. We altered expression of the miR-30 microRNA family and generated phenotypes that mimicked misregulation of the Hedgehog pathway. Inhibition of the miR-30 family increases activity of the pathway, resulting in elevated ptc1 expression and increased numbers of superficial slow-muscle fibres. We show that the transmembrane receptor smoothened is a target of this microRNA family. Our results indicate that fine coordination of smoothened activity by the miR-30 family allows the correct specification and differentiation of distinct muscle cell types during zebrafish embryonic development.
authors.affiliation: Centre for Genetics and Genomics, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Ami
authors.initials: A
authors.lastname: Ketley
authors.forename: Anne
authors.initials: A
authors.lastname: Warren
authors.forename: Emily
authors.initials: E
authors.lastname: Holmes
authors.forename: Martin
authors.initials: M
authors.lastname: Gering
authors.forename: A Aziz
authors.initials: AA
authors.lastname: Aboobaker
authors.forename: J David
authors.initials: JD
authors.lastname: Brook
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019521:Body Patterning / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000378:metabolism*; D008565:Membrane Proteins; D035683:MicroRNAs / Q000235:genetics*; D024510:Muscle Development / Q000235:genetics*; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D000072086:Smoothened Receptor; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D053823:Hedgehog Proteins; C585572:MIRN30 microRNA, zebrafish; D008565:Membrane Proteins; D035683:MicroRNAs; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D000072086:Smoothened Receptor; D029961:Zebrafish Proteins; C491715:ptch1 protein, zebrafish; C491021:smo protein, zebrafish