Whitlock, K.E. and Westerfield, M. (1998) A transient population of neurons pioneers the olfactory pathway in the zebrafish. The Journal of neuroscience : the official journal of the Society for Neuroscience. 18:8919-8927.
Mechanisms guiding the first axons from the olfactory placode of the peripheral 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 receptor genes. Not only are the pioneers antigenically, morphologically, and spatially distinct from olfactory sensory neurons, they are also developmentally 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 necessary connection from the PNS to the CNS and that they establish an axonal scaffold for the later-arriving olfactory sensory neurons.