Thesis (Ph.D) --Murdoch University, 2004. / Thesis submitted to the Division of Health Sciences. Includes bibliographical references (leaves 328-352).

Thesis (Ph.D.)--Murdoch University, 2004. / Thesis submitted to the Division of Health Sciences. Bibliography: leaves 276-318.

Thesis (M. Med. Sc.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 40-51).

Thesis (M.Phil.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 133-138). Also available in print.

Thesis (M.Med.Sc.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 40-51). Also available in print.

Thesis (M.S.)--West Virginia University, 2005. / Title from document title page. Document formatted into pages; contains viii, 99 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 82-99).

published_or_final_version / abstract / Biochemistry / Doctoral / Doctor of Philosophy

published_or_final_version / Surgery / Master / Master of Philosophy

The homeobox superfamily is one of the most significant gene families in the evolution of developmental processes in animals. Within this superfamily the ANTP class has expanded exclusively in animals and, therefore, the reconstruction of its origin and diversification into the different ‘modern' families have become prominent questions in the ‘evo-devo' field. The current burgeoning availability of animal genome sequences is improving the resolution of these questions, putting them in a genome evolution context, as well as providing the field with a large, detailed and diverse catalogue of animal homeobox complements. Here I have contributed with a new hypothesis on the origin and evolution of the Hox and ParaHox loci and the new term, ghost loci, referring to homologous genome regions that have lost their homeobox genes. This hypothesis proposes that the last common ancestor of all animals had a much more complex genome (i.e. differentiated Hox, ParaHox and NK loci) that underwent a simplification in the early animal lineages of sponges and placozoans. In collaboration with the Adamska group I resolved the orthology of the first ever ParaHox genes reported in calcareous sponges. This finding serves as an independent confirmation of the ghost loci hypothesis and further resolves the events of secondary simplification within the sponge lineage. Finally, I have catalogued the homeobox complement of the newly sequenced arthropod, the myriapod Strigamia maritima, and examined the linkage and clustering of these genes. This has furthered our understanding of the evolution of the ANTP class. The diversity of the homeobox complement and the retention in this myriapod and the retention of some homeobox genes not previously described within arthropods, in combination with the interesting phylogenetic position that this lineage occupies relative to other arthropods, makes this complement an important point of reference for comparison within the arthropods and in a broader perspective in the ecdyzosoans. These findings have provided significant further insights into the origin and evolution of the homeobox superfamily, with important implications for animal evolution and the evolution of development.

Câncer e desenvolvimento embrionário possuem diversos aspectos em comum, pois ambos exibem alternância entre proliferação e diferenciação celular. A família dos genes homeobox codifica fatores de transcrição fundamentais para o adequado desenvolvimento embrionário, e têm sido descritos em diferentes neoplasias. O PMX1 (Paired Mesoderm Homeobox 1) é um gene homeobox que está expresso durante o desenvolvimento de diversos tecidos mesenquimais, como o sistema cardiovascular e elementos do esqueleto. A relação entre o PMX1 e neoplasias malignas ainda não está bem estabelecida. O objetivo desse trabalho foi verificar a presença dos transcritos do gene PMX1 em carcinomas epidermóides de boca e tecidos não tumorais adjacentes. Foi realizada hibridização in situ com sondas marcadas com digoxigenina em dezesseis amostras de carcinoma epidemóide de boca e dez de tecido não tumoral adjacente. No tecido não tumoral adjacente o sinal de hibridização é mais intenso nas camadas basal e suprabasal, mesmo quando ele pode ser observado em outras camadas. No carcinoma epidermóide de boca, o sinal está disperso por todo o tecido sendo mais intenso em áreas com células isoladas. Nossos resultados mostram a presença dos transcritos do PMX1 em epitélio de boca e em carcinoma epidermóide de boca e sugerem a participação do gene PMX1 na carcinogênese de boca. A sua expressão em neoplasias pouco diferenciadas deve ser melhor analisada / Cancer and development share common features since both processes exhibit shifts between cell proliferation and differentiation. Homeobox gene family encodes transcription factors essentials for appropriate embryonic development and they have been described in different types of neoplastic tissues. PMX1 (Paired Mesoderm Homeobox 1) is homeobox gene that has been related with mesenchyma throughout development such cardiovascular system and skeletal elements, however its relation with tumor development is not well established yet. The purpose of this study was to verify the presence of PMX1 transcripts in oral squamous cell carcinomas and adjacent non-tumoral tissues. In situ hybridization was performed with probes labeled with digoxigenin in sixteen samples of squamous cell carcinoma and ten o adjacent non-tumoral tissues. In the adjacent non-tumoral tissues in situ hybridization signaling detected were more intense in the basal and parabasal layers even when it could be observed in other layers. In the oral squamous cell carcinoma the signaling was spread all over the tissue becoming more intense in areas with isolated carcinoma cells. Our findings show PMX1 transcripts in adjacent non-tumoral tissues and oral squamous cell carcinoma and suggest participation of PMX1 in oral carcinogenesis. Its expression in poorly differentiated carcinomas needs to be analyzed in detail