Pattern formation in the central nervous system of the zebrafish (Danio rerio) (neurogenesis)

The complex and exquisitely-patterned vertebrate central nervous system (CNS) arises from inductive interactions. The zebrafish (Danio rerio) CNS is relatively simple and optically translucent, well-suited for the direct analysis of cellular interactions critical to neural patterning. The studies in this thesis investigate the early spatial and temporal aspects of induction, morphogenesis, and commitment of the zebrafish CNS. Two detailed fate maps of the CNS are created at the beginning (6 hours) and the end (10 hours) of gastrulation, when regional patterning of the CNS occurs. These fate maps provide the foundation for tests of commitment, where progenitors of different brain regions are transplanted to ectopic locations. Analyses of the progenitor distributions and cell movements within the presumptive neurectoderm show that by the time dorsoventral orientation of the embryo can be recognized (shield-stage), the neurectoderm already displays a predictable organization that reflects the future anteroposterior and dorsoventral order of the CNS. Transplantation results show, however, that this coherent organization within the neurectoderm at shield-stage does not reflect cell-fate commitment, as many brain regions can be readily interconverted at this time. There appears to be regional differences among progenitor domains: While some forebrain progenitors may be committed to the neural fate at shield-stage, hindbrain progenitors appear to undergo neural and regional commitment at mid-gastrulation. Information of the temporal aspect of regional commitment leads to the hypothesis that signals from the non-axial mesendoderm may play a role in posterior (hindbrain) neural patterning. This hypothesis is supported by the observation that forebrain precursors, when juxtaposed with non-axial mesendoderm, are transformed into hindbrain structures. A zebrafish model modified from an amphibian anteroposterior patterning model is postulated to account for these results. Forebrain morphogenesis is examined using cell-marking techniques and video microscopy. These studies show that both retinas originate from a single medial domain that is split by the rostral movement of ventral diencephalon progenitors initially located posterior to the retinal precursors. These, and other observations, highlight the importance of cell and tissue movements, in addition to gene regulations, in patterning the zebrafish anterior nervous system.