A TRANSIENT POPULATION OF NEURONS PIONEERS THE OLFACTORY PATHWAY IN THE ZEBRAFISH

Mechanisms guiding the first axons from the olfactory placode of the p eripheral nervous system (PNS) to the olfactory bulb in the vertebrate CNS are unknown. We analyzed the initial outgrowth of axons from the olfactory placode in zebrafish and found a precocious transient class of pioneer neurons that prefigure the primary olfactory pathway before outgrowth of olfactory sensory axons or expression of olfactory recep tor genes. Not only are the pioneers antigenically, morphologically, a nd spatially distinct from olfactory sensory neurons, they are also de velopmentally distinct; via fate mapping, we show that they arise from a more anterior region of the lateral neural plate than do the first sensory neurons. After the axons of the sensory neurons grow into the CNS, the pioneer neurons undergo apoptotic cell death. When we ablated the pioneers before axonogenesis, the following sensory axons showed severe misrouting. We propose that the pioneers provide the first nece ssary connection from the PNS to the CNS and that they establish an ax onal scaffold for the later-arriving olfactory sensory neurons.