Netrin-1/DCC signaling in commissural axon guidance requires cell-autonomous expression of heparan sulfate

Yoshihiro Matsumoto, Fumitoshi Irie, Masaru Inatani, Marc Tessier-Lavigne, Yu Yamaguchi

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)

Abstract

There is increasing evidence that heparan sulfate (HS) plays an essential role in various axon guidance processes. These observations, however, have not addressed whether HS is required cell autonomously as an axonal coreceptor or as an environmental factor that modulates the localization of guidance molecules in the terrain in which growing axons navigate. Here we demonstrate that netrin-1-mediated commissural axon guidance requires cell-autonomous expression of HS in commissural neurons in vivo. We used the Wnt1 -Cre transgene to drive region-specific ablation of Ext1, which encodes an enzyme essential for HS synthesis, in the dorsal part of the spinal cord. Remarkably, Wnt1-Cre-mediated ablation of Ext1 causes commissural axon pathfinding defects that share similarities with those of Netrin-1-deficient and DCC (deleted in colorectal cancer)-deficient mice. Neither Ext1-deficient dorsal spinal cord explants nor wild-type explants in which HS expression was ablated could extend axons in response to netrin-1. Intracellular signaling downstream of netrin-1 and DCC was defective in Ext1-deficient commissural neurons and in DCC-transfected HEK293T cells from which HS was removed. These results demonstrate that the expression of HS by commissural neurons is essential for these neurons to transduce netrin-1 signals, thus providing evidence for a cell-autonomous role of HS in netrin-1/DCC-mediated axon guidance.

Original languageEnglish
Pages (from-to)4342-4350
Number of pages9
JournalJournal of Neuroscience
Volume27
Issue number16
DOIs
Publication statusPublished - Apr 18 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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