Modulators of axonal growth and guidance at the brain midline with special reference to glial heparan sulfate proteoglycans

Abstract

Bilaterally symmetric organisms need to exchange information between the left and right sides of their bodies to integrate sensory input and to coordinate motor control. Thus, an important choice point for developing axons is the Central Nervous System (CNS) midline. Crossing of this choice point is influenced by highly conserved, soluble or membrane-bound molecules such as the L1 subfamily, laminin, netrins, slits, semaphorins, Eph-receptors and ephrins, etc. Furthermore, there is much circumstantial evidence for a role of proteoglycans (PGs) or their glycosaminoglycan (GAG) moieties on axonal growth and guidance, most of which was derived from simplified models. A model of intermediate complexity is that of cocultures of young neurons and astroglial carpets (confluent cultures) obtained from medial and lateral sectors of the embryonic rodent midbrain soon after formation of its commissures. Neurite production in these cocultures reveals that, irrespective of the previous location of neurons in the midbrain, medial astrocytes exerted an inhibitory or nonpermissive effect on neuritic growth that was correlated to a higher content of both heparan and chondroitin sulfates (HS and CS). Treatment with GAG lyases shows minor effects of CS and discloses a major inhibitory or non-permissive role for HS. The results are discussed in terms of available knowledge on the binding of HSPGs to interative proteins and underscore the importance of understanding glial polysaccharide arrays in addition to its protein complement for a better understanding of neuron-glial interactions.

Interactive properties of human glioblastoma cells with brain neurons in culture and neuronal modulation of glial laminin organization

“…Four distinct immunoreactive patterns can be organized in developing rat brain: small and large punctiform laminin, sheath laminin, and somal laminin on the ECM (Zhou, 1990) with unique spatial and temporal distributions. Our previous study demonstrated that fibrillar or punctuate glial‐ECM laminin organization is related to different degrees of neurite extension (Garcia‐Abreu et al, 1995a; Freire et al, 2002; for a review, see Cavalcante et al, 2002). Here, we verified that levels of laminin expression seem to be higher in Gbm than in glial cells.…”

The Indispensable Roles of Microglia and Astrocytes during Brain Development

“…During early embryonic CNS development in the drosophila, glial cells were found to express the chemo-attractant netrin (Jacobs, 2000) and the chemorepellents Slit and semaphorin (Kidd et al, 1999), all three necessary for accurate axon navigation and midline crossing of commissural axons (Kidd et al, 1998). In vertebrates, glial-like floor plate cells of the spinal cord, Cajal-Retzius cells, subplate cells, and oligodendrocytes precursor cells (OPCs) have been suggested to take part in this prenatal guidance role (Cavalcante et al, 2002; Goldberg et al, 2004), but a role for microglia and astrocytes cannot be excluded either and will be discussed here.…”

Glial Cell-Axonal Growth Cone Interactions in Neurodevelopment and Regeneration

“…Glia have the ability to either directly interact with growing axons through cell adhesion or indirectly by secreting factors that modulate the local microenvironment to promote or inhibit axon growth. Many glial subtypes have been demonstrated to directly impact axon growth and guidance including microglia (Reemst et al, 2016), oligodendrocytes (Chen et al, 2002a;Gang et al, 2015), astrocytes (Cavalcante et al, 2002;Liu R. et al, 2015), Schwann cells (Thompson and Buettner, 2006;De Luca et al, 2015), neural progenitor cells (Merianda et al, 2017), and olfactory ensheathing cells (Windus et al, 2010), and they can either promote or inhibit growth depending on the circumstance. Expanding the knowledge of how different supporting cell types may directly or indirectly interact with growing axons will offer a deeper understanding of the intercellular crosstalk occurring in neurodevelopment, as well as provide clinically useful information, such as identifying potential drugs to modulate neuron regeneration (De Luca et al, 2015;Gang et al, 2015).…”