This work is intended to increase our understanding of the development of the optic chiasm and tract. The projection from the retina to the brain is essential for sight, and the highly ordered nature of the axons' trajectories and terminations are key to the formation of connections that make spatial vision possible. The retinofugal projection is thought to resemble all central nervous system projections, so a study of its development relates to central nervous system development generally. Developmental disorders can not be understood without knowledge of the normal developmental processes, and this proposal is intended to reveal them. It is an anatomical study in which light and electron microscopy and immunocytochemistry are used to study three key players. First, the formation of the projection is initiated by a small set of """"""""pioneer"""""""" axons originating from 5-10 ganglion cells in the retina; experiments in this proposal should elucidate their role in leading the vastly more numerous axons that follow them. Second, the retinal axons pass alongside a pre-existing tract in the brain on their way to the optic tectum; the work proposed here will reveal more about that pre-existing tract and about its role in guiding the growing axons. Third, a structurally distinct zone alongside the pre-existing tract has recently been discovered, and this is where the retinal axons grow; the work here will investigate the importance of that zone in guiding the axons and assess the generality of such a structure for other cases of axonal guidance. Most of the work is carried out in the embryonic zebrafish (Brachydanio rerio), chosen because of its technical advantages and because early development is thought to be very similar in all vertebrates. Where possible, the conclusions will be checked in other vertebrates: frog, chick, and mouse.
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