Moderate repulsive effects of E-unit-containing chondroitin sulfate (CSE) on behavior of retinal growth cones

Shimbo, Miki; Ando, Satoru; Sugiura, Norío; Kimata, Koji; Ichijo, Hiroyuki

doi:10.1016/j.brainres.2012.11.011

Cited by 12 publications

(10 citation statements)

References 60 publications

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“…The CS-E motif has been shown to exert strong inhibitory effects on sensory neurons both in vitro and in vivo (Brown et al, 2012; Gilbert et al, 2005; Karumbaiah et al, 2011; Shimbo et al, 2013). Studies using CS-E-enriched polysaccharides and pure synthetic polymers containing CS-E showed that the CS-E motif was sufficient to inhibit CGN and DRG neurons in neurite outgrowth, growth cone collapse, and boundary assays (Brown et al, 2012; Gilbert et al, 2005; Shimbo et al, 2013). In contrast, CS-A- and CS-C-enriched polysaccharides and synthetic polymers had no appreciable inhibitory effects even when used at 10-fold higher concentrations or when combined with CS-E.…”

Section: Cspgs As Inhibitory Cues For Neuronal Growthmentioning

confidence: 99%

Sugar-dependent modulation of neuronal development, regeneration, and plasticity by chondroitin sulfate proteoglycans

Miller

Hsieh‐Wilson

2015

Experimental Neurology

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Chondroitin sulfate proteoglycans (CSPGs) play important roles in the developing and mature nervous system, where they guide axons, maintain stable connections, restrict synaptic plasticity, and prevent axon regeneration following CNS injury. The chondroitin sulfate glycosaminoglycan (CS GAG) chains that decorate CSPGs are essential for their functions. Through these sugar chains, CSPGs are able to bind and regulate the activity of a diverse range of proteins. CSPGs have been found both to promote and inhibit neuronal growth. They can promote neurite outgrowth by binding to various growth factors such as midkine (MK), pleiotrophin (PTN), brain-derived neurotrophic factor (BDNF) and other neurotrophin family members. CSPGs can also inhibit neuronal growth and limit plasticity by interacting with transmembrane receptors such as protein tyrosine phosphatase σ (PTPσ), leukocyte common antigen-related (LAR) receptor protein tyrosine phosphatase, and the Nogo receptors 1 and 3 (NgR1 and NgR3). These CS-protein interactions depend on specific sulfation patterns within the CS GAG chains, and accordingly, particular CS sulfation motifs are upregulated during development, in the mature nervous system, and in response to CNS injury. Thus, spatiotemporal regulation of CS GAG biosynthesis may provide an important mechanism to control the functions of CSPGs and to modulate intracellular signaling pathways. Here, we will discuss these sulfation-dependent processes and highlight how the CS sugars on CSPGs contribute to neuronal growth, axon guidance, and plasticity in the nervous system.

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Section: Cspgs As Inhibitory Cues For Neuronal Growthmentioning

confidence: 99%

Sugar-dependent modulation of neuronal development, regeneration, and plasticity by chondroitin sulfate proteoglycans

Miller

Hsieh‐Wilson

2015

Experimental Neurology

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“…This method, the "CS-PE beads assay" enables Simbo et al to compare effects of CS with different structural diversity on the behavior of retinal growth cones directly in time-lapse movies ( Figure 4) [49]. Growth cones of the retinal ganglion cells avoided E-unit containing CS-PE beads (CSE-PE beads), exhibiting significant repulsion or turning away from the CSE-PE beads.…”

Section: Lipid-derivatized Chondroitin Sulfate and Polystyrene Beads mentioning

confidence: 99%

Application of Chondroitin Sulfate Derivatives for Understanding Axonal Guidance in the Nervous System during Development

2013

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Neuronal axons and their growth cones recognize molecular guidance cues within the local environment, forming axonal pathways to produce precise neuronal networks during nervous system development. Chondroitin sulfates (CS), carbohydrate chains on chondroitin sulfate proteoglycans, exhibit great structural diversity and exert various influences on axons and growth cones as guidance cues or their modulators; however, the relationship between their structural diversity and function in axonal guidance is not well known. To uncover the roles of CS in axonal guidance, artificially modified hybrid molecules: CS derivatives of biotinylated CS and lipid-derivatized CS, were used. The experiments with biotinylated CS suggest that the growing axons act on their environment, modifying CS, and rendering it more favorable for their growth. The experiments with lipid-derivatized CS demonstrated that growth cones distinguish types of CS with different unit contents and are likely to discriminate the structural diversity of CS. The application of CS derivatives is useful in uncovering axon-environment interaction and structure-function relationship of CS directly.

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“…12 Some literature reports either dispute the functional significance of the sulfation motifs present in CS chains or provide contradictory evidence for the role of sulfation variants in neuronal regeneration, plasticity, and recovery. 12–17 Recently, Brown et al addressed this by chemically synthesizing homogeneous glycopolymers of CS-A, CS-C, and CS-E disaccharide motifs and examining their role in axonal regeneration. 18 By culturing DRG neurons on substrates containing such covalently bound glycopolymers, they showed that CS-E glycopolymers inhibited neurite outgrowth, while CS-A and CS-C had minimal activity.…”

Section: Introductionmentioning

confidence: 99%

Exploiting Differential Surface Display of Chondroitin Sulfate Variants for Directing Neuronal Outgrowth

et al. 2013

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Chondroitin sulfate (CS) proteoglycans (CSPGs) are known to be primary inhibitors of neuronal regeneration at scar sites. However, a variety of CSPGs are also involved in neuronal growth and guidance during other physiological stages. Sulfation patterns of CS chains influence their interactions with various growth factors in the central nervous system (CNS), thus influencing neuronal growth, inhibition, and pathfinding. This report demonstrates the use of differentially sulfated CS chains for neuronal navigation. Surface-immobilized patterns of CS glycosaminoglycan chains were used to determine neuronal preference toward specific sulfations of five CS variants: CS-A, CS-B (dermatan sulfate), CS-C, CS-D, and CS-E. Neurons preferred CS-A, CS-B, and CS-E and avoided CS-C containing lanes. In addition, significant alignment of neurites was observed using underlying lanes containing CS-A, CS-B, and CS-E chains. To utilize differential preference of neurons toward the CS variants, a binary combinations of CS chains were created by backfilling a neuro-preferred CS variant between the microcontact printed lanes of CS-C stripes, which are avoided by neurons. The neuronal outgrowth results demonstrate for the first time that a combination of sulfation variants of CS chains without any protein component of CSPG is sufficient for directing neuronal outgrowth. Biomaterials with surface immobilized GAG chains could find numerous applications as bridging devices for tackling CNS injuries where directional growth of neurons is critical for recovery.

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Moderate repulsive effects of E-unit-containing chondroitin sulfate (CSE) on behavior of retinal growth cones

Cited by 12 publications

References 60 publications

Sugar-dependent modulation of neuronal development, regeneration, and plasticity by chondroitin sulfate proteoglycans

Sugar-dependent modulation of neuronal development, regeneration, and plasticity by chondroitin sulfate proteoglycans

Application of Chondroitin Sulfate Derivatives for Understanding Axonal Guidance in the Nervous System during Development

Exploiting Differential Surface Display of Chondroitin Sulfate Variants for Directing Neuronal Outgrowth

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