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Mammalian brain morphogenesis and midline axon guidance require heparan sulfate.

Heparan sulfate (HS) is required for morphogen signaling during Drosophila pattern formation, but little is known about its physiological importance in mammalian development. To define the developmental role of HS in mammalian species, we conditionally disrupted the HS-polymerizing enzyme EXT1 in the embryonic mouse brain. The EXT1-null brain exhibited patterning defects that are composites of those caused by mutations of multiple HS-binding morphogens. Furthermore, the EXT1-null brain displayed severe guidance errors in major commissural tracts, revealing a pivotal role of HS in midline axon guidance. These findings demonstrate that HS is essential for mammalian brain development.

Pubmed ID: 14605369


  • Inatani M
  • Irie F
  • Plump AS
  • Tessier-Lavigne M
  • Yamaguchi Y


Science (New York, N.Y.)

Publication Data

November 7, 2003

Associated Grants

  • Agency: NICHD NIH HHS, Id: P01 HD25938
  • Agency: NINDS NIH HHS, Id: R01 NS33117

Mesh Terms

  • Animals
  • Axons
  • Body Patterning
  • Brain
  • Cerebellum
  • Cerebral Cortex
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors
  • Heparitin Sulfate
  • Homeodomain Proteins
  • Inferior Colliculi
  • Intercellular Signaling Peptides and Proteins
  • Mesencephalon
  • Mice
  • Mice, Knockout
  • Morphogenesis
  • Mutation
  • N-Acetylglucosaminyltransferases
  • Nerve Tissue Proteins
  • Optic Chiasm
  • Proto-Oncogene Proteins
  • Retina
  • Rhombencephalon
  • Signal Transduction
  • Wnt Proteins
  • Zebrafish Proteins