DYNAMICS OF MASH1 EXPRESSION IN-VITRO AND IN-VIVO SUGGEST A NON-STEM CELL SITE OF MASH1 ACTION IN THE OLFACTORY RECEPTOR NEURON LINEAGE

Disruption of the mouse gene encoding the transcription factor MASH1 l eads to loss of certain classes of neurons, including receptor neurons of the olfactory epithelium (OE). Here we investigate the nature of t he cell type expressing MASH1 in mouse OE by manipulating olfactory re ceptor neuron (ORN) neurogenesis in vitro and in vivo to alter the dyn amics of neuronal production. The results indicate that MASH1 is expre ssed in cells of the ORN lineage, but not in ORNs themselves nor in th eir immediate precursors. Data on how changes in the numbers and proli ferative states of MASH1(+) cells correlate with induced changes in ov erall neurogenesis strongly suggest that MASH1-expressing cells give r ise to the immediate precursors of ORNs, but are not the self-renewing stem cells of the DE. The results imply that multiple progenitor stag es are employed in generating ORNs and suggest that the action of MASH 1 occurs predominantly at an intermediate stage.