Sulfated proteoglycans as modulators of neuronal migration and axonal decussation in the developing midbrain

Abstract

Proteoglycans are abundant in the developing brain and there is much circumstantial evidence for their roles in directional neuronal movements such as cell body migration and axonal growth. We have developed an in vitro model of astrocyte cultures of the lateral and medial sectors of the embryonic mouse midbrain, that differ in their ability to support neuritic growth of young midbrain neurons, and we have searched for the role of interactive proteins and proteoglycans in this model. Neurite production in co-cultures reveals that, irrespective of the previous location of neurons in the midbrain, medial astrocytes exert an inhibitory or nonpermissive effect on neuritic growth that is correlated to a higher content of both heparan and chondroitin sulfates (HS and CS). Treatment of astrocytes with chondroitinase ABC revealed a growth-promoting effect of CS on lateral glia but treatment with exogenous CS-4 indicated a U-shaped dose-response curve for CS. In contrast, the growth-inhibitory action of medial astrocytes was reversed by exogenous CS-4. Treatment of astrocytes with heparitinase indicated that the growth-inhibitory action of medial astrocytes may depend heavily on HS by an as yet unknown mechanism. The results are discussed in terms of available knowledge on the binding of HS proteoglycans to interactive proteins, with emphasis on the importance of unraveling the physiological functions of glial glycoconjugates for a better understanding of neuron-glial interactions.

Evaluation of Chondroitin Sulfate Bioactivity in Hippocampal Neurones and the Astrocyte Cell Line U373: Influence of Position of Sulfate Groups and Charge Density

“…This astrocyte cell line synthesizes extracellular matrix that has been suggested to play a role in neuritic migratory extension (Kearns et al 2003). They exert an inhibitory or nonpermissive effect on neuritic growth that is correlated to a higher content of both heparan and chondroitin sulfates (Cavalcante et al 2003). Thus, due to astrocytic involvement in chondroitin sulfate proteoglycans generation for neuronal guidance, astrocytes may be insensitive for chondroitin sulfate chain signaling.…”

Immune Infiltration Associated MAN2B1 Is a Novel Prognostic Biomarker for Glioma

“…For example, glycolipids and proteoglycans participate in the constructions and physiological functions of neurons and glial cells in brain tissue. In addition, glycoconjugates are involved in cell proliferation, differentiation, cell-cell interaction, and signal transmission (10,11). Thus, many glycoconjugates have been recommended and approved by FDA as biomarkers to identify a given disease condition and monitor patients undergoing therapy clinically (12).…”

Arylsulfatase B Improves Locomotor Function after Mouse Spinal Cord Injury

“…Among molecules identified in many studies to inhibit growth are members of the chondroitin sulfate proteoglycan (CSPG) family, which are up-regulated in expression in the injured parts of the central nervous system [5]–[7]. CSPGs are mostly localized in the extracellular matrix and are major formative determinants during nervous system development [8]–[11]. Their importance in synaptic functions and plasticity in the adult is increasingly becoming recognized, particularly regarding the striking structures of perineuronal nets whose contributions to interneuronal activity have been mainly unresolved, but are thought to limit plasticity [12]–[14].…”