Axon guidance and target interactions in the developing trigeminal system

During the formation of the nervous system axons extend long distances in order to reach the appropriate target. Sensory growth cones respond to many cues in the periphery; they may be attractive or repulsive, diffusable or membrane bound. During the course of this dissertation a number of cues that play important roles in axon guidance and target interactions in the developing trigeminal system will be examined. In the rat, sensory trigeminal axons elongate from the trigeminal ganglia (TG) into the periphery where they enter the whisker pad, amongst other targets, in a tightly fasciculated bundle and then fan out in a caudal to rostral direction. Whisker row nerves display a centrifugal dispersion from their point of entry into the whisker pad, a patterned array is seen where nerves form dense, cup-shaped plexuses associated with the sensory receptors of follicles. This pattern of innervation can be duplicated in culture.; Axons in the rodent trigeminal pathway invade the developing whisker pad from a caudal to rostral direction due to spatially expressed effectors of axon guidance. Embryonic day (E) 15 trigeminal axons readily grew into same age whisker pad explants and formed follicle-related patterns in a caudal to rostral direction, but were unable to invade the whisker pad from the rostral (nasal) pole. There are age-related changes in trigeminal axon responsiveness to directional cues. E19 trigeminal axons readily grew into E15 whisker pad explants from either the caudal or the rostral pole.; Trigeminal axons from rodent and avian species behave similarly when cocultured with chick maxillary process or rat whisker pad. Specific patterning of TG axons in the rodent whisker pad is not an intrinsic characteristic of the rodent trigeminal axons, but is largely determined by target-derived axon-guidance cues. In culture conditions trigeminal ganglia from E5 chick were seen to increase in size when placed with E15 whisker pad. This effect was duplicated by the addition of exogenously added nerve growth factor (NGF).; Slit2 has been shown to exhibit a branching effect in E15 brainstem TG preparations [Ozdinler, 2001 #363] and in situ hybridization showed slit2 to be expressed in the whisker pad during the arrival of trigeminal axons to the follicle sinus complex (FSC). In peripheral cocultures utilizing E12 presumptive whisker pad and TG of varying age branching due to increased levels of slit2 was not seen. Additionally, high levels of robo-fc's in E15 whisker pad TG cocultures were unable to decrease branching.; In peripheral development it is the target tissue that is most important, the target tissue is the producer of signals that are expressed in a spatio-temporal manner. These signals display an evolutionarily conserved mechanism of axon guidance.