ZFIN ID: ZDB-PUB-060616-49
Hhip regulates zebrafish muscle development by both sequestering Hedgehog and modulating localization of Smoothened
Ochi, H., Pearson, B.J., Chuang, P.T., Hammerschmidt, M., and Westerfield, M.
Date: 2006
Source: Developmental Biology   297(1): 127-140 (Journal)
Registered Authors: Hammerschmidt, Matthias, Ochi, Haruki, Pearson, Bret, Westerfield, Monte
Keywords: Clathrin, Endosomes, Hedgehog signaling, Patched, Skeletal muscle, Smoothened, Zebrafish
MeSH Terms:
  • Animals
  • Cell Membrane/metabolism
  • Drosophila Proteins/genetics
  • Drosophila Proteins/metabolism
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism*
  • Muscle Development*
  • Muscles/cytology
  • Muscles/embryology
  • Protein Structure, Tertiary
  • Receptors, Cell Surface/genetics
  • Receptors, Cell Surface/metabolism
  • Receptors, G-Protein-Coupled/genetics
  • Receptors, G-Protein-Coupled/metabolism*
  • Sequence Homology, Amino Acid
  • Trans-Activators/genetics
  • Trans-Activators/metabolism*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 16765934 Full text @ Dev. Biol.
Sharp borders between cells with different developmental fates are important for patterning of invertebrates, but are not well understood in vertebrates. Zebrafish slow muscle cells develop from adaxial cells, a one-cell-diameter-thick pseudo-epithelium immediately adjacent to the notochord. Hedgehog (Hh) signals from notochord specify adaxial cells to form slow muscle cells. Cells next to adaxial cells form fast muscle. This suggests that Hh signaling is locally regulated to produce a sharp border that separates slow and fast muscle precursors. To understand how Hh activity is locally regulated, we characterized the dynamic roles of Hhip, a protein that binds Hedgehog at the cell surface. Hhip is strongly expressed by adaxial cells and, together with Patched, the Hedgehog receptor, limits transduction of the Hedgehog signaling by Smoothened to adaxial cells. Hhip protein lacking its membrane associated domain still suppresses Hh activity but no longer acts synergistically with Patched. Hhip and Smoothened colocalize at the cell surface and, in response to Hedgehog, internalize together. Knockdown of Hhip blocks Smoothened internalization while increasing Hedgehog signaling and slow muscle formation. These data support a model in which Hhip regulates muscle development both by sequestering Hedgehog and by modulating localization of Smoothened.