The cell surface carbohydrate blood group A regulates the selective fasciculation of regenerating accessory olfactory axons

Abstract

Cell surface carbohydrates are differentially expressed by discrete subpopulations of primary sensory axons in the mammalian main and accessory olfactory systems. It has been proposed that these carbohydrates provide a glycocode which mediates the sorting of these sensory axons as they project from the olfactory neuroepithelium to their central targets in the main and accessory olfactory bulbs during development. As the differential expression of cell surface carbohydrates on olfactory axons persists in the adult we have now investigated their role during regeneration. We have recently generated a line of transgenic mice, BGAT-Tg, that mis-express the blood group A (BGA) carbohydrate on all primary olfactory axons rather than just on accessory olfactory axons as in wild-type mice. Following unilateral bulbectomy, accessory and main olfactory axons regenerate and grow into the frontal cortex where they fill the cavity which remains after the olfactory bulb ablation. In wild-type mice, the regenerating BGA-expressing accessory olfactory axons selectively aggregated with each other in large bundles but clearly separated from the BGA-negative main olfactory axons. In contrast, in the BGAT-Tg transgenic mice in which all main and accessory axons express the BGA carbohydrate, the accessory olfactory axons failed to correctly separate from the main olfactory axons. Instead, these axons formed numerous small bundles interspersed with main olfactory axons. These data provide strong evidence that the restricted expression of BGA is in part responsible for the selective segregation of accessory olfactory axons.