Long-range Sclerotome Induction by Sonic Hedgehog: Direct Role of the Amino-Terminal Cleavage Product and Modulation by the Cyclic AMP Signaling Pathway

Cell. 1995 May 5;81(3):457-65. doi: 10.1016/0092-8674(95)90398-4.

Abstract

A long-range signal encoded by the Sonic hedgehog (Shh) gene has been implicated as the ventral patterning influence from the notochord that induces sclerotome and represses dermomyotome in somite differentiation. Long-range effects of hedgehog (hh) signaling have been suggested to result either from local induction of a secondary diffusible signal or from the direct action of the highly diffusible carboxy-terminal product of HH autoproteolytic cleavage. Here we provide evidence that the long-range somite patterning effects of SHH are instead mediated by a direct action of the amino-terminal cleavage product. We also show that pharmacological manipulations to increase the activity of cyclic AMP-dependent protein kinase A can selectively antagonize the effects of the amino-terminal cleavage product. Our results support the operation of a single evolutionarily conserved signaling pathway for both local and direct long-range inductive actions of HH family members.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biomarkers
  • Bone and Bones / embryology*
  • Cell Communication*
  • Cells, Cultured
  • Chick Embryo
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Embryonic Induction*
  • Hedgehog Proteins
  • Mesoderm / physiology
  • Mice
  • Mitogens
  • Muscles / embryology
  • Peptide Fragments / physiology
  • Proteins / metabolism
  • Proteins / physiology*
  • Recombinant Proteins / metabolism
  • Ribs / embryology
  • Signal Transduction*
  • Skin / embryology
  • Spine / embryology
  • Trans-Activators*

Substances

  • Biomarkers
  • Hedgehog Proteins
  • Mitogens
  • Peptide Fragments
  • Proteins
  • Recombinant Proteins
  • Trans-Activators
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases