Integrated interactions between chondroitin sulphate proteoglycans and weak dc electric fields regulate nerve growth cone guidance in vitro

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Abstract

During development and regenerative growth, neuronal pathways are defined in part by several endogenous cues that collectively determine directed growth. The interactions between such cues largely are unknown. To address potential interactions, we have examined in vitro the combined effect on nerve growth of two endogenous growth cone guidance cues: chondroitin sulphate proteoglycans and weak dc electric fields. Addition to the culture medium of a chondroitin 6-sulphate/keratan sulphate containing PG (BNC-PG) markedly enhanced the cathodal re-orientation of embryonic Xenopus neurites in an electric field, whereas a proteoglycan containing chondroitin 4-sulphate (RC-PG) was inhibitory. These effects of BNC-PG and RC-PG were reproduced by their chondroitin sulphate glycosaminoglycan side chains alone. Chondroitin 6-sulphate or chondroitin 4-sulphate, respectively, enhanced and inhibited cathodally-directed nerve re-orientation. This was dependent on the integrity of the glycosaminoglycan chain structure; when digested into their disaccharide subunits both molecules became inactive. Keratan sulphate, a minor component of BNC-PG, was found to be inhibitory, whereas dermatan sulphate, an epimer of chondroitin 4-sulphate, had no effect. We conclude that in vitro specific interactions between these two nerve guidance cues do occur and that the specificity of the response is critically dependent on the charge pattern of the proteoglycans chondroitin sulphate side chains. The expression of a host of proteoglycans with differing glycosaminoglycan side chains varies in both time and place in the developing nervous system, thus the scope is vast for spatial and temporal modulation of nerve guidance by interacting cues.
Original languageEnglish
Pages (from-to)1957-1965
Number of pages9
JournalJournal of Cell Science
Volume110
Issue number16
Publication statusPublished - 1 Aug 1997

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Chondroitin Sulfate Proteoglycans
Growth Cones
Chondroitin Sulfates
Cues
Keratan Sulfate
Glycosaminoglycans
Dermatan Sulfate
Disaccharides
Neurites
Proteoglycans
Growth
Xenopus
Growth and Development
Nervous System
Culture Media
In Vitro Techniques

Keywords

  • Animals
  • Carbohydrate Conformation
  • Chondroitin Sulfates
  • Dermatan Sulfate
  • Disaccharides
  • Electric Stimulation
  • Embryo, Nonmammalian
  • Keratan Sulfate
  • Kinetics
  • Nervous System
  • Neurites
  • Neurons
  • Proteochondroitin Sulfates
  • Xenopus laevis
  • Development
  • Glycosaminoglycan,
  • Axon guidance

Cite this

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title = "Integrated interactions between chondroitin sulphate proteoglycans and weak dc electric fields regulate nerve growth cone guidance in vitro",
abstract = "During development and regenerative growth, neuronal pathways are defined in part by several endogenous cues that collectively determine directed growth. The interactions between such cues largely are unknown. To address potential interactions, we have examined in vitro the combined effect on nerve growth of two endogenous growth cone guidance cues: chondroitin sulphate proteoglycans and weak dc electric fields. Addition to the culture medium of a chondroitin 6-sulphate/keratan sulphate containing PG (BNC-PG) markedly enhanced the cathodal re-orientation of embryonic Xenopus neurites in an electric field, whereas a proteoglycan containing chondroitin 4-sulphate (RC-PG) was inhibitory. These effects of BNC-PG and RC-PG were reproduced by their chondroitin sulphate glycosaminoglycan side chains alone. Chondroitin 6-sulphate or chondroitin 4-sulphate, respectively, enhanced and inhibited cathodally-directed nerve re-orientation. This was dependent on the integrity of the glycosaminoglycan chain structure; when digested into their disaccharide subunits both molecules became inactive. Keratan sulphate, a minor component of BNC-PG, was found to be inhibitory, whereas dermatan sulphate, an epimer of chondroitin 4-sulphate, had no effect. We conclude that in vitro specific interactions between these two nerve guidance cues do occur and that the specificity of the response is critically dependent on the charge pattern of the proteoglycans chondroitin sulphate side chains. The expression of a host of proteoglycans with differing glycosaminoglycan side chains varies in both time and place in the developing nervous system, thus the scope is vast for spatial and temporal modulation of nerve guidance by interacting cues.",
keywords = "Animals, Carbohydrate Conformation, Chondroitin Sulfates, Dermatan Sulfate, Disaccharides, Electric Stimulation, Embryo, Nonmammalian, Keratan Sulfate, Kinetics, Nervous System, Neurites, Neurons, Proteochondroitin Sulfates, Xenopus laevis, Development, Glycosaminoglycan,, Axon guidance",
author = "Lynda Erskine and McCaig, {Colin Darnley}",
year = "1997",
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day = "1",
language = "English",
volume = "110",
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TY - JOUR

T1 - Integrated interactions between chondroitin sulphate proteoglycans and weak dc electric fields regulate nerve growth cone guidance in vitro

AU - Erskine, Lynda

AU - McCaig, Colin Darnley

PY - 1997/8/1

Y1 - 1997/8/1

N2 - During development and regenerative growth, neuronal pathways are defined in part by several endogenous cues that collectively determine directed growth. The interactions between such cues largely are unknown. To address potential interactions, we have examined in vitro the combined effect on nerve growth of two endogenous growth cone guidance cues: chondroitin sulphate proteoglycans and weak dc electric fields. Addition to the culture medium of a chondroitin 6-sulphate/keratan sulphate containing PG (BNC-PG) markedly enhanced the cathodal re-orientation of embryonic Xenopus neurites in an electric field, whereas a proteoglycan containing chondroitin 4-sulphate (RC-PG) was inhibitory. These effects of BNC-PG and RC-PG were reproduced by their chondroitin sulphate glycosaminoglycan side chains alone. Chondroitin 6-sulphate or chondroitin 4-sulphate, respectively, enhanced and inhibited cathodally-directed nerve re-orientation. This was dependent on the integrity of the glycosaminoglycan chain structure; when digested into their disaccharide subunits both molecules became inactive. Keratan sulphate, a minor component of BNC-PG, was found to be inhibitory, whereas dermatan sulphate, an epimer of chondroitin 4-sulphate, had no effect. We conclude that in vitro specific interactions between these two nerve guidance cues do occur and that the specificity of the response is critically dependent on the charge pattern of the proteoglycans chondroitin sulphate side chains. The expression of a host of proteoglycans with differing glycosaminoglycan side chains varies in both time and place in the developing nervous system, thus the scope is vast for spatial and temporal modulation of nerve guidance by interacting cues.

AB - During development and regenerative growth, neuronal pathways are defined in part by several endogenous cues that collectively determine directed growth. The interactions between such cues largely are unknown. To address potential interactions, we have examined in vitro the combined effect on nerve growth of two endogenous growth cone guidance cues: chondroitin sulphate proteoglycans and weak dc electric fields. Addition to the culture medium of a chondroitin 6-sulphate/keratan sulphate containing PG (BNC-PG) markedly enhanced the cathodal re-orientation of embryonic Xenopus neurites in an electric field, whereas a proteoglycan containing chondroitin 4-sulphate (RC-PG) was inhibitory. These effects of BNC-PG and RC-PG were reproduced by their chondroitin sulphate glycosaminoglycan side chains alone. Chondroitin 6-sulphate or chondroitin 4-sulphate, respectively, enhanced and inhibited cathodally-directed nerve re-orientation. This was dependent on the integrity of the glycosaminoglycan chain structure; when digested into their disaccharide subunits both molecules became inactive. Keratan sulphate, a minor component of BNC-PG, was found to be inhibitory, whereas dermatan sulphate, an epimer of chondroitin 4-sulphate, had no effect. We conclude that in vitro specific interactions between these two nerve guidance cues do occur and that the specificity of the response is critically dependent on the charge pattern of the proteoglycans chondroitin sulphate side chains. The expression of a host of proteoglycans with differing glycosaminoglycan side chains varies in both time and place in the developing nervous system, thus the scope is vast for spatial and temporal modulation of nerve guidance by interacting cues.

KW - Animals

KW - Carbohydrate Conformation

KW - Chondroitin Sulfates

KW - Dermatan Sulfate

KW - Disaccharides

KW - Electric Stimulation

KW - Embryo, Nonmammalian

KW - Keratan Sulfate

KW - Kinetics

KW - Nervous System

KW - Neurites

KW - Neurons

KW - Proteochondroitin Sulfates

KW - Xenopus laevis

KW - Development

KW - Glycosaminoglycan,

KW - Axon guidance

M3 - Article

VL - 110

SP - 1957

EP - 1965

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 16

ER -