Patterning the embryonic brain: multiple signals converge to establish spatial identity within a neuromeric field

Lake, Blue B. (2004) Patterning the embryonic brain: multiple signals converge to establish spatial identity within a neuromeric field. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

Precisely arranged signaling events are required to establish the immense complexity of the embryonic central nervous system. During gastrulation, as the organizing mesendoderm endows neural identity on the overlying ectoderm, it concurrently initiates differential specification along the anterior-posterior (AP) neuraxis by antagonizing caudalizing signals. Upon completion of the embryonic germ layer rearrangements of the late gastrulae, the prospective neural plate shows primitive AP identity, which must be extensively rearranged and refined during neurula and tadpole stages by organizing centers occurring in adjacent tissues (mesendoderm and non-neural ectoderm) as well as within both the dorsoventral (roof plate and floorplate) and AP (anterior neural ridge and isthmic organizer) plane of the neurectoderm. Signals along both axes establish a grid-like network of gene expression providing the spatial cues for a cell to adopt its precisely choreographed differentiation program. Perturbations to components of this network result in severely abnormal phenotypes, thereby providing information on their function. I have utilized this approach to determine the requirements of both a Xenopus Rel/NF-κβ protein (Xrel3) and two novel components of the intracellular Wnt/β-Catenin signal transduction cascade (XPygo-2α/β) in morphogenesis of brain and optic vesicles. Xrel3 specifies both fore-midbrain and ventral identity of the nervous system by regulating otx2 and shh/glil gene expression, while both XPygo-2α and XPygo-2β mediate a late phase of Wnt signaling required to establish retinal and telencephalic domains of gene expression within the prospective forebrain.

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