Dally-like core protein and its mammalian homologues mediate stimulatory and inhibitory effects on Hedgehog signal response

Elizabeth H. Williams, William N. Pappano, Adam M. Saunders, Min Sung Kim, Daniel J. Leahy, Philip A. Beachy

Research output: Contribution to journalArticlepeer-review

Abstract

The distribution and activities of morphogenic signaling proteins such as Hedgehog (Hh) and Wingless (Wg) depend on heparan sulfate proteoglycans (HSPGs). HSPGs consist of a core protein with covalently attached heparan sulfate glycosaminoglycan (GAG) chains. We report that the unmodified core protein of Dally-like (Dlp), an HSPG required for cell-autonomous Hh response in Drosophila embryos, alone suffices to rescue embryonic Hh signaling defects. Membrane tethering but not specifically the glycosylphos-phatidylinositol linkage characteristic of glypicans is critical for this cell-autonomous activity. Our studies further suggest divergence of the two Drosophila and six mammalian glypicans into two functional families, an activating family that rescues cell-autonomous Dlp function in Hh response and a family that inhibits Hh response. Thus, in addition to the previously established requirement for HSPG GAG chains in Hh movement, these findings demonstrate a positive cell-autonomous role for a core protein in morphogen response in vivo and suggest the conservation of a network of antagonistic glypican activities in the regulation of Hh response.

Original languageEnglish (US)
Pages (from-to)5869-5874
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number13
DOIs
StatePublished - Mar 30 2010

Keywords

  • Glypicans
  • Heparan sulfate proteoglycans

ASJC Scopus subject areas

  • General

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