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• W1993608710 abstract "The presentation of secreted axon guidance factors plays a major role in shaping central nervous system (CNS) connectivity [1Dickson B.J Molecular mechanisms of axon guidance.Science. 2002; 298: 1959-1964Crossref PubMed Scopus (1113) Google Scholar]. 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 [2Bernfield M Gotte M Park P.W Reizes O Fitzgerald M.L Lincecum J Zako M Functions of cell surface heparan sulfate proteoglycans.Annu. Rev. Biochem. 1999; 68: 729-777Crossref PubMed Scopus (2233) Google Scholar, 3Lander A.D Selleck S.B The elusive functions of proteoglycans in vivo veritas.J. Cell Biol. 2000; 148: 227-232Crossref PubMed Scopus (213) Google Scholar, 4Yamaguchi Y Heparan sulfate proteoglycans in the nervous system their diverse roles in neurogenesis, axon guidance, and synaptogenesis.Semin. Cell Dev. Biol. 2001; 12: 99-106Crossref PubMed Scopus (120) Google Scholar]. 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, consistent with the localization of Sdc to CNS axons. sdc mutants exhibit consistent defects in midline axon guidance, plus potent and specific genetic interactions supporting a model in which HSPGs improve the efficiency of Slit localization and/or signaling. To test this hypothesis, we show that Slit distribution is altered in sdc mutants and that Slit and its receptor bind to Sdc. However, when we compare the function of the transmembrane Sdc to a different class of HSPG that localizes to CNS axons (Dallylike), we find functional redundancy, suggesting that these proteoglycans act as spatially specific carriers of common HS structures that enable growth cones to interact with and perceive Slit as it diffuses away from its source at the CNS midline." @default.
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• W1993608710 date "2004-03-01" @default.
• W1993608710 modified "2023-10-16" @default.
• W1993608710 title "Axonal Heparan Sulfate Proteoglycans Regulate the Distribution and Efficiency of the Repellent Slit during Midline Axon Guidance" @default.
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• W1993608710 doi "https://doi.org/10.1016/j.cub.2004.02.005" @default.
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