Hedgehog signalling acts upstream of Laminin alpha1 transcription in the zebrafish paraxial mesoderm

• Published in: Matrix biology 2017-10, Vol.62, p.58-74
• Main Authors: Pickering, Joseph, Cunliffe, Vincent T., Van Eeden, Freek, Borycki, Anne-Gaëlle
• Format: Article
• Language: English
• Subjects: Animals; Animals, Genetically Modified; Basement membranes; Binding Sites; Cell fate; Danio rerio; Embryo; Embryogenesis; Embryology; Enhancer Elements, Genetic; Enhancers; Extracellular matrix; Gene expression; Gene Expression Regulation, Developmental; Gene regulation; Hedgehog protein; Hedgehog Proteins - metabolism; Hedgehog signalling; Hindbrain; Introns; Laminin; Laminin - chemistry; Laminin - genetics; Laminin - metabolism; Mesoderm; Mesoderm - growth & development; Mesoderm - metabolism; Morphogenesis; Pattern formation; Promoter Regions, Genetic; Proteins; Signal Transduction; Spinal cord; Transcription; Transcription, Genetic; Zebrafish; Zebrafish - genetics; Zebrafish - growth & development; Zebrafish - metabolism; Zebrafish Proteins - chemistry; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism
• ISSN: 0945-053X; 1569-1802
• DOI: 10.1016/j.matbio.2016.11.004

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. •A transgenic line, lama1:GFP, recapitulates the expression pattern of lama1 in the zebrafish embryo.•Hedgehog signalling is necessary and sufficient to drive lama1 expression in the zebrafish paraxial mesoderm.•An intronic enhancer controls lama1 transcription in the paraxial mesoderm and anterior CNS.•lama1 intronic enhancer activity is regulated by Hedgehog signalling.