Evidence that pioneer olfactory axons regulate telencephalon cell cycle kinetics to induce the formation of the olfactory bulb.

Early olfactory axons follow a specific pathway to reach the developing telencephalon. We observed that a subpopulation of these axons, the pioneer olfactory axons, penetrate into the ventricular zone of a highly restricted region of the telencephalon at E13 and E14. At E15, this same telencephalic region evaginates to form the olfactory bulb. To investigate the possibility that the pioneer olfactory axons induce the olfactory bulb by influencing precursor cell populations, we compared cell cycle kinetics and differentiation in the olfactory bulb primordium and the adjacent neocortex using cumulative bromdeoxyuridine labeling. The results showed that, 24 hr after the arrival of the first pioneer axons, the duration of the cell cycle is prolonged significantly in the olfactory bulb primordium. In addition, twice as many cells have exited the mitotic cycle in the olfactory bulb primordium versus the adjacent cortex. These findings suggest that pioneer olfactory axons play a role in the induction of the olfactory bulb by selectively modulating cell cycle kinetics in the olfactory bulb primordium. Afferent axons may influence target morphogenesis by modulating target precursor cell proliferation in other developing neural structures.