Date of Award

2008

Degree Type

Thesis

Degree Name

Doctor of Philosophy

Faculty

Faculty of Computing, Health and Science

First Advisor

Associate Professor Mel Ziman

Second Advisor

Associate Professor Frank J. Lovicu

Abstract

This thesis has explored the role of Pax7 in formation and maturation of the mouse superior colliculus, an important brain region associated with topographic visual input and the capacity to evoke appropriate visuomotor responses to environmental stimuli. The research performed was explicitly targeted at understanding the relationship between Pax7 expression and the formation of the topography of the superior colliculus, including neuron specification and differentiation, boundary formation, polarisation and retinocollicular mapping. By employing histochemical, immunohistochemical and immunofluorescent techniques, together with quantification utilising Optimas Digital Image Analysis, this project assessed Pax7 expression in diverse mutant and wildtype mice throughout a variety of developmental timepoints. Quantification revealed dynamic Pax7 expression patterns consisting of gradients of both cellular distribution and cellular protein levels, which act in summation to polarise the superior colliculus. Graded Pax7 cellular distribution and protein levels are optimal during retinal innervation and axon arborisation in wildtype mice. This contrasts with that of Pax6 mutant mice which demonstrate reduced Pax7 protein levels as a result of optic nerve hypoplasia. These results demonstrate a responsive role for Pax7 in retinocollicular mapping, and therefore visual system development. Examination of Pax7 mutant mice divulged a greater understanding of the role of Pax7 during superior collicular development, and provided the first determination of central nervous system defects in Pax7 mutant animals. Results indicate that Pax7 is redundant for neuronal specification and differentiation, but is requisite, in a dosage-dependent manner, for maintenance of a subpopulation of dorsal superior collicular neurons and subsequently superior collicular polarity. The paralogue Pax3 is thought responsible for sustaining embryonic development in Pax7 mutant mice, resulting in a less severe phenotype. Therefore, this project explored temporospatial patterns of Pax3 expression relative to Pax7 expression during all embryonic stages examined. Findings detail a diverging expression pattern between paralogues that is spatially and temporally associated with neuronal differentiation and maturation within the superior colliculus. Moreover, Pax3 expression is spatially perturbed within the central nervous system of Pax7 mutant mice, exhibiting changes in the time at which Pax3-expressing cells exit from the germinal region. The results of the research undertaken in this thesis have significantly contributed to the understanding of developmental mechanisms occurring within the superior colliculus, and the contribution of Pax7 to these processes. Findings delineate that the functional repertoire of Pax7 within the superior colliculus embraces neuronal maturation and maintenance, determination of polarity and participation in retinocollicular mapping.

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