Scube activity is necessary for Hedgehog signal transduction in vivo

Dev Biol. 2012 Aug 15;368(2):193-202. doi: 10.1016/j.ydbio.2012.05.007. Epub 2012 May 17.

Abstract

The Hedgehog (HH) signaling pathway is a central regulator of embryonic development, controlling the pattern and proliferation of a wide variety of organs. Previous studies have implicated the secreted protein, Scube2, in HH signal transduction in the zebrafish embryo (Hollway et al., 2006; Kawakami et al., 2005; Woods and Talbot, 2005) although the nature of the molecular function of Scube2 in this process has remained undefined. This analysis has been compounded by the fact that removal of Scube2 activity in the zebrafish embryo leads to only subtle defects in HH signal transduction in vivo (Barresi et al., 2000; Hollway et al., 2006; Ochi and Westerfield, 2007; van Eeden et al., 1996; Wolff et al., 2003). Here we present the discovery of two additional scube genes in zebrafish, scube1 and scube3, and demonstrate their roles in facilitating HH signal transduction. Knocking down the function of all three scube genes simultaneously phenocopies a complete loss of HH signal transduction in the embryo, revealing that Scube signaling is essential for HH signal transduction in vivo. We further define the molecular role of scube2 in HH signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • COS Cells
  • Calcium-Binding Proteins / genetics*
  • Calcium-Binding Proteins / metabolism
  • Chlorocebus aethiops
  • DNA, Complementary / chemistry
  • DNA, Complementary / genetics
  • Embryo, Nonmammalian / embryology
  • Embryo, Nonmammalian / metabolism*
  • Extracellular Matrix Proteins / genetics*
  • Extracellular Matrix Proteins / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Hedgehog Proteins / genetics*
  • Hedgehog Proteins / metabolism
  • In Situ Hybridization
  • Molecular Sequence Data
  • Multigene Family
  • Mutation
  • Phenotype
  • Sequence Analysis, DNA
  • Signal Transduction / genetics*
  • Zebrafish / embryology
  • Zebrafish / genetics
  • Zebrafish / metabolism
  • Zebrafish Proteins / genetics*
  • Zebrafish Proteins / metabolism

Substances

  • Calcium-Binding Proteins
  • DNA, Complementary
  • Extracellular Matrix Proteins
  • Hedgehog Proteins
  • Scube1 protein, zebrafish
  • Scube2 protein, zebrafish
  • Zebrafish Proteins

Associated data

  • GENBANK/JF900367
  • GENBANK/JF900368