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Science 302 (5647): 1044-1046

Copyright © 2003 by the American Association for the Advancement of Science

Mammalian Brain Morphogenesis and Midline Axon Guidance Require Heparan Sulfate

Masaru Inatani,1 Fumitoshi Irie,1 Andrew S. Plump,2* Marc Tessier-Lavigne,2{dagger} Yu Yamaguchi1{ddagger}

Abstract: 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.

1 The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
2 Department of Biological Sciences, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94035, USA.

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* Present address: Merck Research Laboratories, 126 Lincoln Avenue, Rahway, NJ 07065, USA.

{dagger} Present address: Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

{ddagger} To whom correspondence should be addressed. E-mail: yyamaguchi{at}burnham.org

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