Secretion of the amino-terminal fragment of the hedgehog protein is necessary and sufficient for hedgehog signalling in Drosophila

Curr Biol. 1995 Jun 1;5(6):643-50. doi: 10.1016/s0960-9822(95)00129-1.

Abstract

Background: The Drosophila segment polarity gene hedgehog encodes a member of a family of secreted proteins that are involved in a variety of patterning processes, in both vertebrates and invertebrates. Some of these processes depend upon short-range or contact-dependent interactions, whereas others seem to involve long-range signalling. Two different models have been proposed to account for the execution of these contrasting processes by the same proteins: one postulates that Hedgehog acts exclusively over short distances, its long-range influences being effected through regulation of other signalling factors; the second postulates that different aspects of Hedgehog activity are mediated by distinct forms of the protein that are generated by autoproteolysis.

Results: We have investigated these models by mutating the hedgehog coding region such that only the amino-terminal or carboxy-terminal half of the protein is secreted. Deletion of the carboxy-terminal portion has little effect on the signalling activity of the protein, whereas abolishing the secretion of the amino-terminal half leads to a complete loss of signalling. In addition, we find that increases in the level of expression within the normal hedgehog transcriptional domain of either the wild-type protein or the carboxy-terminal-deleted form expand the range of activity to a limited extent, but have only minor effects on cell identity.

Conclusions: In Drosophila, all of the signalling activity of Hedgehog resides in the amino-terminal portion of the protein, the secretion of which is essential for its function. The range of Hedgehog is limited by the close association of the amino-terminal peptide with the cell surface but can be extended by elevating the level of its expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Drosophila Proteins*
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology*
  • Gene Expression Regulation
  • Hedgehog Proteins
  • Insect Hormones / physiology
  • Larva
  • Molecular Sequence Data
  • Morphogenesis / genetics
  • Peptide Fragments / physiology*
  • Proteins / chemistry
  • Proteins / physiology*
  • Recombinant Proteins / metabolism
  • Signal Transduction*
  • Transcription, Genetic
  • Wings, Animal / embryology
  • Wings, Animal / growth & development

Substances

  • Drosophila Proteins
  • Hedgehog Proteins
  • Insect Hormones
  • Peptide Fragments
  • Proteins
  • Recombinant Proteins
  • dpp protein, Drosophila
  • hh protein, Drosophila