ADULT OLFACTORY EPITHELIUM CONTAINS MULTIPOTENT PROGENITORS THAT GIVERISE TO NEURONS AND NONNEURAL CELLS

We have infused replication-incompetent retroviral vectors into the na sal cavity of adult rats 1 day after exposure to the olfactotoxic gas methyl bromide (MeBr) to assess the lineage relationships of cells in the regenerating olfactory epithelium. The vast majority of the retrov irus-labeled clones fall into three broad categories: clones that inva riably contain globose basal cells (GBCs) and/or neurons, clones that always include cells in the ducts of Bowman's glands, and clones that are composed of sustentacular cells only, Many of the GBC-related clon es contain sustentacular cells and horizontal basal cells as well. Mos t of the duct-related clones contain gland cells, and some also includ e sustentacular cells. Thus, the destruction of both neurons and non-n euronal cells that is caused by MeBr activates two distinct types of m ultipotent cells. The multipotent progenitor that gives rise to neuron s and non-neuronal cells is a basal cell, whereas the progenitor that gives rise to duct, gland, and sustentacular cells resides within the ducts, based on the pattern of sparing after lesion and the analysis o f early regeneration by using cell type-specific markers. We conclude that the balance between multipotency and selective neuropotency, whic h is characteristic of globose basal cells in the normal olfactory epi thelium, is determined by which cell types have been depleted and need to be replenished rapidly. (C) 1998 Wiley-Liss, Inc.