Sugar Codes for Axons?
Abstract
potential for extraordinary diversity. Several recent studies have demonstrated important roles for heparan sulfate and chondroitin sulfate proteoglycans (HSPGs and CSPGs) in axon pathfinding and have linked HSPGs to specific signaling pathways. More speculatively, there are hints of a “sugar code,” in which specific sugar modifications might act instructively in guidance decisions. This raises the intriguing possibility that the complexity of neuronal wiring may in part reflect the complexity of proteoglycan modifications.
The first hints that heparan sulfate proteoglycans (HSPGs) might have important functions in axon guidance came with the demonstration that enzymatic removal of heparan sulfate causes severe pathfinding defects by pioneering axons in the developing cockroach limb bud (Wang and Denburg, 1992). Subsequent studies also revealed roles for HS in axon navigation in the vertebrate visual system (Halfter, 1993; Irie et al., 2002; Walz et al., 1997). Over this same period, evidence began to accumulate suggesting that chondroitin sulfate proteoglycans (CSPGs) also influence neurite outgrowth in vitro (Snow et al., 1991) and contribute to axon pathfinding in vivo (Brittis et al., 1992; Walz et al., 2002). Now, a recent spate of studies in a variety of different organisms—mice, fish, flies, and worms—has provided compelling genetic evidence that proteoglycans are, indeed, key players in axon guidance in vivo and offered the first intriguing insights into the molecular pathways in which they act. This minireview will focus mainly on HSPGs, but will also briefly discuss recent genetic evidence showing that CSPGs may play a similarly complex and important role in axon guidance.