Glycoconjugates in Cell-Cell Interactions
During the past 5 years several significant findings have been made. We have shown that the ventral mid-line of the olfactory bulb plays a unique role in axon guidance, and it is special glial cells (ensheathing cells) that produce specific proteins in this region that are key factors in development of the olfactory's system. Axons begin to grow from the OE to the OB around E11 in the mouse, but patterning of the system begins in earnest around E13. At this time ventral ensheathing cells produce proteins that are secreted into the surrounding extracellular matrix (ECM). One protein is galectin-1, an extracellular carbohydrate-binding protein that interacts with other proteins in the ECM and with a carbohydrate on axons named lactosamine-containing glycan (LCG). One of the interacting proteins is laminin, also produced and secreted by ensheathing cells. Laminin is a heterotrimer composed of 3 chains. Interestingly one of those chains, B-1 laminin is produced in excessive amounts by ensheathing cells in the ventral nerve layer. We predict that this unique laminin chain distribution in the nerve layer of the OB plays an important role in creating permissive regions of the nerve layer for axon subsets. For example, we have shown that LCG+ axon grow preferentially into the ventromedial nerve layer through the region in which B1-laminin and galectin-1 are heavily expressed. The axon fibers are surrounded by B-1 laminin/galectin-1 giving the impression that the channels are uniquely produced for this axon subset.
We have recently shown that another protein, Semaphorin-3A, (Sema3A) is also produced by ensheathing cells in the nerve layer of the ventral OB. Axons that express the receptor, neuropilin-1, are repelled by Sema3A and thus grow into regions of the OB in which Sema3A is absent. This finding, that ensheathing cells in the ventral OB produce proteins that are permissive to growth by some axons and non-permissive to growth by other axons is novel, and has implications for the patterning of connections throughout the developing nervous system.