Pioneer neurons in the mouse trigeminal sensory system.

Pioneer neurons establish preliminary nerve pathways that are followed by later-growing axons. The existence of pioneers and their importance is well documented in invertebrate systems. In mammals, early neuronal development has generally been difficult to study because of the size and complexity of the embryos, and the lack of adequate markers. Here we look at the time of earliest axonal outgrowth in the mouse embryo by using specific monoclonal antibodies to stain wholemount preparations. During the period of formation and closure of the neuropore beginning at embryonic day 8.5, we can follow the earliest trigeminal sensory neurons extending axons along stereotyped pathways. In the trigeminal ganglion, an early wave of neurogenesis gives rise to a small number of neurons whose axons pioneer the different trigeminal tracts in the periphery. After a brief pause (12 hr), these primary axons branch out to innervate individual targets. Emerging a day later, secondary fibers extend along the pioneers. By contrast, in the central nervous system, neurons of the mesencephalic trigeminal nucleus extend toward the rhombencephalon independently, ignoring preexisting fibers. These results show the existence of an early set of axonal tracts in the mouse peripheral nervous system that may be used for the guidance of later-differentiating neurons.