Versican in the Developing Brain: Lamina-Specific Expression in Interneuronal Subsets and Role in Presynaptic Maturation

Abstract

Chondroitin sulfate proteoglycans (CSPGs) of the extracellular matrix help stabilize synaptic connections in the postnatal brain and impede regeneration after injury. Here, we show that a CSPG of the lectican family, versican, also promotes presynaptic maturation in the developing brain. In the embryonic chick optic tectum, versican is expressed selectively by subsets of interneurons confined to the retinorecipient laminae, in which retinal axons arborize and form synapses. It is a major receptor for the Vicia villosa B 4 lectin (VVA), shown previously to inhibit invasion of the retinorecipient lamina by retinal axons (Inoue and Sanes, 1997). In vitro, versican promotes enlargement of presynaptic varicosities in retinal axons. Depletion of versican in ovo, by RNA interference, results in retinal arbors with smaller than normal varicosities. We propose that versican provides a lamina-specific cue for presynaptic maturation and discuss the related but distinct effects of versican depletion and VVA blockade.

Target-Derived Cues Instruct Synaptic Differentiation: Figure 1.

“…Although the majority of previous findings show that versican is made by glia, double-label in situ hybridization showed that, in the embryonic chick tectum, versican is expressed by local interneurons that also express reelin, substance-P receptor, or neuropilin-1 but not by cells expressing the glial marker glutamine synthetase. These experiments also revealed that versican expression is graded across the depth of the tectal layers [Yamagata and Sanes, (2005) (Fig. 1), which could have implications for layer-specific axon guidance.…”

“…A recent article by Yamagata and Sanes in The Journal of Neuroscience [Yamagata and Sanes, (2005) (http://www/jneurosci. org/cgi/content/full/25/37/8457)] provides new insights into these questions.…”

“…What sorts of cues guide RGC axons to their correct layer? The recent work of Yamagata and Sanes (2005) was prompted by their previous findings that the plant lectin Vicia villosa agglutinin B4 (VVA-B4) selectively binds the retinorecipient layers. VVA-B4 recognizes N-acetylgalactosaminyl (GalNAc) residues, cell-surface carbohydrates that are typically found as components of the extracellular matrix.…”

“…To identify the tectal proteins that bind VVA-B4, Yamagata and Sanes (2005) used a biochemical approach in which they homogenized hundreds of chick tecta and applied that material to a VVA-B4-containing column. Then they isolated and purified the proteins that bound VVA-B4, by elution with GalNAc.…”

“…Then they isolated and purified the proteins that bound VVA-B4, by elution with GalNAc. Analysis of the purified proteins with mass spectography revealed that all were lecticantype proteoglycans derived from agrin, aggrecan, or versican [Yamagata and Sanes (2005) What type of cells express versican? Although the majority of previous findings show that versican is made by glia, double-label in situ hybridization showed that, in the embryonic chick tectum, versican is expressed by local interneurons that also express reelin, substance-P receptor, or neuropilin-1 but not by cells expressing the glial marker glutamine synthetase.…”