Cerebellar proteoglycans regulate sonic hedgehog responses during development

  • Rubin J
  • Choi Y
  • Segal R
  • 54

    Readers

    Mendeley users who have this article in their library.
  • 114

    Citations

    Citations of this article.

Abstract

Sonic hedgehog promotes proliferation of developing cerebellar granule cells. As sonic hedgehog is expressed in the cerebellum throughout life it is not clear why proliferation occurs only in the early postnatal period and only in the external granule cell layer. We asked whether heparan sulfate proteoglycans might regulate sonic hedgehog-induced proliferation and thereby contribute to the specialized proliferative environment of the external granule cell layer. We identified a conserved sequence within sonic hedgehog that is essential for binding to heparan sulfate proteoglycans, but not for binding to the receptor patched. Sonic hedgehog interactions with heparan sulfate proteoglycans promote maximal proliferation of postnatal day 6 granule cells. By contrast, proliferation of less mature granule cells is not affected by sonic hedgehog-proteoglycan interactions. The importance of proteoglycans for proliferation increases during development in parallel with increasing expression of the glycosyltransferase genes, exostosin 1 and exostosin 2. These data suggest that heparan sulfate proteoglycans, synthesized by exostosins, may be critical determinants of granule cell proliferation.

Author-supplied keywords

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • COS Cells
  • Cell Division
  • Cells: Cultured
  • Cerebellum
  • Hedgehog Proteins
  • Heparan Sulfate Proteoglycans
  • Heparin
  • Mice
  • Mice: Inbred BALB C
  • Molecular Sequence Data
  • Mutation
  • N-Acetylglucosaminyltransferases
  • Protein Structure: Tertiary
  • Proteins
  • Sequence Homology: Amino Acid
  • Trans-Activators
  • Transfection

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

  • PMID: 11959830
  • PUI: 34879062
  • ISBN: 0950-1991
  • ISSN: 1477-9129
  • SGR: 0036341998
  • SCOPUS: 2-s2.0-0036341998

Authors

  • J B Rubin

  • Y Choi

  • R A Segal

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free