Mammalian Brain Morphogenesis and Midline Axon Guidance Require Heparan Sulfate

• DOI: 10.1126/science.1090497
• Publication Date: 2003-11-06T22:23:30Z
• Authors: Masaru Inatani; Fumitoshi Irie; Andrew S. Plump; Marc Tessier-Lavigne; Yu Yamaguchi
• Keywords: Cerebral Cortex; Homeodomain Proteins; Mice, Knockout; 0301 basic medicine; Fibroblast Growth Factor 8; Brain; Nerve Tissue Proteins; N-Acetylglucosaminyltransferases; Axons; Inferior Colliculi; Fibroblast Growth Factors; Mice; 03 medical and health sciences; Mesencephalon; Cerebellum; Optic Chiasm; Mutation; Morphogenesis; Animals; Intercellular Signaling Peptides and Proteins; Heparitin Sulfate; Body Patterning

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.