title: The zebrafish-secreted matrix protein you/scube2 is implicated in long-range regulation of hedgehog signaling.
abstract: The Hedgehog (Hh) signal plays a pivotal role in induction of ventral neuronal and muscle cell types around the midline during vertebrate development [1]. We report that the gene disrupted in zebrafish you mutants, in which Hh signaling is impaired, encodes the secreted matrix protein Scube2. Consistently, epistasis analyses suggested that Scube2 functions upstream of Hh ligands or through a parallel pathway. In addition, overexpression analyses suggested that Scube2 is an essential, but a permissive, mediator of Hh signaling in zebrafish embryos. Surprisingly, the you gene is expressed in the dorsal neural tube, raising the possibility that Scube2 could indirectly act via a long-range regulator of Hh signaling. The dorsal Bmps have a long-range and opposing influence on Hh signaling [2-5]. We show that neural plate patterning is affected in you mutants in a way that is consistent with the aberrant long-range action of a Bmp-dependent signal. We further show that Bmp activity can be attenuated by the coexpression of Scube2. Our data support the idea that Scube2 can modulate the long-range action of Bmp-dependent signaling in the neural tube and somites.
authors.affiliation: Department of Biological Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. atkawaka@biol.s.u-tokyo.ac.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawakami
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nojima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Toyoda
authors.forename: Mikako
authors.initials: M
authors.lastname: Takahoko
authors.forename: Miki
authors.initials: M
authors.lastname: Satoh
authors.forename: Hideomi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Hironori
authors.initials: H
authors.lastname: Wada
authors.forename: Ichiro
authors.initials: I
authors.lastname: Masai
authors.forename: Harumi
authors.initials: H
authors.lastname: Terasaki
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Sakaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takeda
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okamoto
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D019521:Body Patterning / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002490:Central Nervous System / Q000196:embryology*; D002874:Chromosome Mapping; D017931:DNA Primers; D004843:Epistasis, Genetic; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D040461:Gene Components; D005838:Genotype; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D053823:Hedgehog Proteins; C500835:Scube2 protein, zebrafish; D015534:Trans-Activators; D029961:Zebrafish Proteins