title: Hedgehog signalling acts upstream of Laminin alpha1 transcription in the zebrafish paraxial mesoderm.
abstract: Laminin-111 (α1β1γ1) is a member of the Laminin family of extra-cellular matrix proteins that comprises 16 members, components of basement membranes. Laminin-111, one of the first Laminin proteins synthesised during embryogenesis, is required for basement membrane deposition and has essential roles in tissue morphogenesis and patterning. Yet, the mechanisms controlling Laminin-111 expression are poorly understood. We generated a zebrafish transgenic reporter line that reproduces faithfully the expression pattern of lama1, the gene encoding Laminin α1, and we used this reporter line to investigate lama1 transcriptional regulation. Our findings established that lama1 expression is controlled by intronic enhancers, including an enhancer directing expression in the paraxial mesoderm, anterior spinal cord and hindbrain, located in intron 1. We show that Hedgehog signalling is necessary and sufficient for lama1 transcription in the paraxial mesoderm and identify putative Gli/Zic binding sites that may mediate this control. These findings uncover a conserved role for Hedgehog signalling in the control of basement membrane assembly via its transcriptional regulation of lama1, and provide a mechanism to coordinate muscle cell fate specification in the zebrafish embryo.
authors.affiliation: Bateson Centre, Department of Biomedical Science, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK.
authors.forename: Joseph
authors.initials: J
authors.lastname: Pickering
authors.affiliation: Bateson Centre, Department of Biomedical Science, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK.
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Cunliffe
authors.affiliation: Bateson Centre, Department of Biomedical Science, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK.
authors.forename: Freek
authors.initials: F
authors.lastname: Van Eeden
authors.affiliation: Bateson Centre, Department of Biomedical Science, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK. Electronic address: a.g.borycki@sheffield.ac.uk.
authors.forename: Anne-Gaëlle
authors.initials: AG
authors.lastname: Borycki
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001665:Binding Sites; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000378:metabolism*; D007438:Introns; D007797:Laminin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008648:Mesoderm / Q000254:growth & development* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D014158:Transcription, Genetic; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D053823:Hedgehog Proteins; D007797:Laminin; D029961:Zebrafish Proteins; C510925:laminin alpha1, zebrafish
keywords: Embryo; Hedgehog signalling; Laminin; Zebrafish