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published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

No description available.

No description available.

No description available.

The Siberian hamster and Fischer 344 (F344) rat exhibit strong natural alterations in body weight that are programmed by the ambient photoperiod and allow preparation for the approaching season, whereby they have a lower body weight in winter-like photoperiods (8 h light per day). The mechanisms that permit this dynamic regulation of body weight may identify novel targets for anti-obesity drugs. Siberian hamster studies involved analysis of photoperiod-driven gene expression changes in the hypothalamic paraventricular nucleus using tissue obtained by laser capture microdissection.  Juvenile F344 rats were susceptible to diet-induced obesity and defended a photoperiod-sensitive rate of lean mass deposition.  In addition, mRNA levels of various genes were found to be photoperiodically regulated in the mediobasal hypothalamus (MBH) including traditional energy balance genes and growth-related genes (e.g. neuropeptide Y and growth hormone releasing hormone). Furthermore, a time course study using Affymetrix arrays was used to analyse the changes in gene expression following 3 d, 14 d and 28 d of exposure to long or short photoperiod in the MBH.  Dramatic changes in gene expression in the thyroid hormone system were found at all time points and confirmed by <i>in situ</i> hybridisation.  The changes found correlated with recent findings in the quail and sheep documenting thyrotropin release from the pituitary regulating thyroid hormone levels in the MBH.  These studies also identified strong photoperiodic regulation of two novel systems related to the thyroid hormone axis; the retinoid and Wnt signalling pathways. Thus, these studies establish the F344 rat as an interesting seasonal animal model and further understanding of the underlying mechanisms of photoperiodism.

Thesis (M.Sc.)--University of the Witwatersrand, Faculty of Science, 1950.

The Hox genes encode a family of evolutionarily conserved transcription factors whose differential expression along head-to-tail triggers distinct programs of cell differentiation along the body axis. Mutations affecting the expression of Hox genes disrupt normal development in animals as diverse as insects and mammals. Although the developmental, evolutionary and biomedical relevance of this gene family is indisputable, the understanding of the molecular mechanisms controlling Hox gene expression is still incomplete. In particular little is known about the ways Hox gene expression is controlled within developmental units such as the insect segments or the rhombomeres in the developing mammalian brain. Previous work in Drosophila showed that different RNA processing events including alternative transcription, alternative splicing and alternative polyadenylation can affect Hox gene expression during the development of complex tissues such as the nervous system showing that differential RNA processing contributes to the generation of elaborate Hox expression patterns in the fruitfly embryo. Here we explore the impact of RNA processing on the molecular functions and developmental expression of Hox genes in mammals. For this we apply a combination of bioinformatic and computational methods complemented by a series of experiments in mammalian cell culture. Our work shows, first, that RNA processing has a pervasive impact on the expression of murine and human Hox genes and that specific Hox RNA processing reactions are coupled to one another and have evolved in coordination with gene-duplication events. Second, we find that RNA processing affecting several independent Hox genes can lead to the generation of Hox protein isoforms that lack a DNA-binding unit (the Homeodomain) suggesting that protein isoforms that are able and unable to bind DNA might be produced during development; furthermore, experiments in cell culture suggest that shorter homeodomain-less isoforms can be generated from longer homeodomain-containing templates suggesting a novel mechanism of RNA processing predicted to substantially impact the biochemical functions of Hox proteins. Third, we find that Hox alternative polyadenylation leading to the production of different 3' untranslated regions (3' UTRs) in Hox mRNAs can explain the generation of complex spatial patterns of Hox expression in the mouse developing limbs and brain. Altogether, our work adds to the current understanding of the molecular control of Hox expression during mammalian development, showing that RNA processing can significantly impact the biochemical properties and expression of Hox proteins.

No description available.

The palaeoecology of selected fossil sites from the Riversleigh World Heritage Area, northwestern Queensland, Australia, was studied with the aim of describing the palaeohabitats of the sites through the use of characteristics of mammalian community structure. Taphonomic analyses were carried out to determine whether the study sites represent allochthonous or autochthonous assemblages. Subsequently, ecological attributes of the mammalian fossil assemblages were inferred from functional morphology. Trophic and locomotor behaviours were used to describe the adaptive structure of communities and a method was established for inferring the locomotor behaviour of fossil taxa from morphometrics of their calcanea. Such ecological attributes of the assemblages can be used in reconstructing habitats. This is possible because modern mammalian community structure (as represented by ecological diversity/attribute characteristics) has been found to correlate with habitat structure and thus has predictive value, directly applicable in palaeoecology. Modern mammalian faunas from a variety of habitats around the world were used as possible analogues for the Riversleigh fossil faunas. Multivariate statistical techniques were explored for identifying potential similarities between the community structure of the fossil faunas and that of the modern faunas. Annual rainfall was then estimated for the fossil sites through regression analysis allowing climatic inference from the faunal palaeocommunities. On the basis of similarities in community structure, general habitat or vegetation structure was proposed for the fossil assemblages. The results of the analyses undertaken indicate that Riversleigh early-middle Miocene habitats were densely forested. The late Oligocene Quantum Leap Site local fauna and the late Miocene Encore Site local fauna suggest mixed vegetation, or more open environments. The trend of decreasing annual rainfall through the Miocene and the palaeohabitats of the Miocene sites proposed here fit the general pattern of vegetation and climate change during this period for the Australian continent as a whole.