title: Expression of multiple slow myosin heavy chain genes reveals a diversity of zebrafish slow twitch muscle fibres with differing requirements for Hedgehog and Prdm1 activity.
abstract: The zebrafish embryo develops a series of anatomically distinct slow twitch muscle fibres that characteristically express genes encoding lineage-specific isoforms of sarcomeric proteins such as MyHC and troponin. We show here that different subsets of these slow fibres express distinct members of a tandem array of slow MyHC genes. The first slow twitch muscle fibres to differentiate, which are specified by the activity of the transcription factor Prdm1 (also called Ubo or Blimp1) in response to Hedgehog (Hh) signalling, express the smyhc1 gene. Subsequently, secondary slow twitch fibres differentiate in most cases independently of Hh activity. We find that although some of these later-forming fibres also express smyhc1, others express smyhc2 or smyhc3. We show that the smyhc1-positive fibres express the ubo (prdm1) gene and adopt fast twitch fibre characteristics in the absence of Prdm1 activity, whereas those that do not express smyhc1 can differentiate independently of Prdm1 function. Conversely, some smyhc2-expressing fibres, although independent of Prdm1 function, require Hh activity to form. The adult trunk slow fibres express smyhc2 and smyhc3, but lack smyhc1 expression. The different slow fibres in the craniofacial muscles variously express smyhc1, smyhc2 and smyhc3, and all differentiate independently of Prdm1.
authors.affiliation: MRC Centre for Developmental and Biomedical Genetics and Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
authors.forename: Stone
authors.initials: S
authors.lastname: Elworthy
authors.forename: Murray
authors.initials: M
authors.lastname: Hargrave
authors.forename: Robert
authors.initials: R
authors.lastname: Knight
authors.forename: Katharina
authors.initials: K
authors.lastname: Mebus
authors.forename: Philip W
authors.initials: PW
authors.lastname: Ingham
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004625:Embryo, Nonmammalian; D019085:Fluorescent Antibody Technique, Direct; D015870:Gene Expression / Q000502:physiology; D018740:Genetic Heterogeneity; D053823:Hedgehog Proteins / Q000235:genetics / Q000502:physiology*; D017403:In Situ Hybridization; D018657:Muscle Fibers, Slow-Twitch / Q000166:cytology / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D019076:Transgenes; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D053823:Hedgehog Proteins; D009687:Nuclear Proteins; D029961:Zebrafish Proteins; D000074462:Positive Regulatory Domain I-Binding Factor 1; C513257:prdm1a protein, zebrafish; D018995:Myosin Heavy Chains