title: Emilin3 is required for notochord sheath integrity and interacts with Scube2 to regulate notochord-derived Hedgehog signals.
abstract: The notochord is a transient and essential structure that provides both mechanical and signaling cues to the developing vertebrate embryo. In teleosts, the notochord is composed of a core of large vacuolated cells and an outer layer of cells that secrete the notochord sheath. In this work, we have identified the extracellular matrix glycoprotein Emilin3 as a novel essential component of the zebrafish notochord sheath. The development of the notochord sheath is impaired in Emilin3 knockdown embryos. The patterning activity of the notochord is also affected by Emilin3, as revealed by the increase of Hedgehog (Hh) signaling in Emilin3-depleted embryos and the decreased Hh signaling in embryos overexpressing Emilin3 in the notochord. In vitro and in vivo experiments indicate that Emilin3 modulates the availability of Hh ligands by interacting with the permissive factor Scube2 in the notochord sheath. Overall, this study reveals a new role for an EMILIN protein and reinforces the concept that structure and function of the notochord are strictly linked.
authors.affiliation: Department of Biomedical Sciences, University of Padova, I-35121 Padova, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Corallo
authors.forename: Alvise
authors.initials: A
authors.lastname: Schiavinato
authors.forename: Valeria
authors.initials: V
authors.lastname: Trapani
authors.forename: Enrico
authors.initials: E
authors.lastname: Moro
authors.forename: Francesco
authors.initials: F
authors.lastname: Argenton
authors.forename: Paolo
authors.initials: P
authors.lastname: Bonaldo
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D060172:Morpholinos / Q000494:pharmacology; D009672:Notochord / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D000954:Antigens, Surface; C585505:Emilin3 protein, zebrafish; D016326:Extracellular Matrix Proteins; D053823:Hedgehog Proteins; D008562:Membrane Glycoproteins; D060172:Morpholinos; C500835:Scube2 protein, zebrafish; D029961:Zebrafish Proteins
keywords: EMILIN; Extracellular matrix; Hedgehog; Notochord; Scube2; Zebrafish