2004
DOI: 10.1016/j.cub.2004.02.005
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Axonal Heparan Sulfate Proteoglycans Regulate the Distribution and Efficiency of the Repellent Slit during Midline Axon Guidance

Abstract: The presentation of secreted axon guidance factors plays a major role in shaping central nervous system (CNS) connectivity. Recent work suggests that heparan sulfate (HS) regulates guidance factor activity; however, the in vivo axon guidance roles of its carrier proteins (heparan sulfate proteoglycans, or HSPGs) are largely unknown. Here we demonstrate through genetic analysis in vivo that the HSPG Syndecan (Sdc) is critical for the fidelity of Slit repellent signaling at the midline of the Drosophila CNS, con… Show more

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Cited by 185 publications
(249 citation statements)
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“…Studies of mutants with impaired HS synthesis and of HSPGs themselves have revealed their essential role in the transport and reception of secreted factors, including Wingless, Hedgehog, Decapentaplegic, Fibroblast Growth Factor (3), and Slit (4,5). Drosophila contains 4 HSPGs: Perlecan (6), Division abnormally delayed (Dally), Dallylike protein (Dlp; 7,8), and Syndecan (Sdc; 4,5).…”
mentioning
confidence: 99%
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“…Studies of mutants with impaired HS synthesis and of HSPGs themselves have revealed their essential role in the transport and reception of secreted factors, including Wingless, Hedgehog, Decapentaplegic, Fibroblast Growth Factor (3), and Slit (4,5). Drosophila contains 4 HSPGs: Perlecan (6), Division abnormally delayed (Dally), Dallylike protein (Dlp; 7,8), and Syndecan (Sdc; 4,5).…”
mentioning
confidence: 99%
“…In Drosophila, Sdc was shown to regulate Slit signaling (4,5). Slit, a secreted ligand produced in ventral midline cells, acts as a repellent in both axon and myotube guidance during embryogenesis, 2 processes that are mediated by Robo receptors in the target cells (18).…”
mentioning
confidence: 99%
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“…Syndecan has been shown to be a ligand for Dlar, a membrane-bound tyrosine phosphatase (Fox and Zinn, 2005;Johnson et al, 2006). Dlar is important in axon guidance at the NMJ (Johnson et al, 2004). Dally-like protein, which is a glypican, has been shown to be important in Wnt signaling, helping to present Wnt to its receptor and creating extracellular gradients of this morphogen (Baeg et al, 2001;Kirkpatrick et al, 2004).…”
Section: Cell Adhesion Moleculesmentioning
confidence: 99%
“…HSPGs are constituents of the cell membrane and extracellular matrix (ECM) that regulate the structural integrity and permeability of the ECM. Furthermore, they bind to and control the biological function of signaling molecules, such as growth factors and morphogens (Allen and Rapraeger, 2003;Johnson et al, 2004;Kreuger et al, 2006). These interactions with signaling molecules underlie in part the importance of HSPGs in development (Lin et al, 1999;Galli et al, 2003;Bornemann et al, 2004).…”
Section: Introductionmentioning
confidence: 99%