The gene capicua is required for the establishment of dorsal-ventral polarity in the Drosophila melanogaster ovary. Loss of capicua function in the follicle cells results in dorsalization of both the embryo and eggshell. The most prominent dorsal features of the Drosophila eggshell are the dorsal appendages. We show that loss of capicua function results in the ventral ectopic specification of dorsal appendage-producing follicle cell fate. This cell fate change is due in part to the ectopic expression of genes such as mirror and Broad-Complex in capicua mutant ovaries. When either mirror or Broad-Complex are ectopically expressed independently of loss of capicua function, they generate a phenotype similar to the capicua mutant phenotype. We propose that Capicua normally acts in the ventral follicle cells to repress the expression of genes that pattern the dorsal follicle cells. EGF receptor signaling may normally inactivate Capicua repression in the dorsal follicle cells.

Evolvable hardware (EHW) uses simulated evolution to generate an electronic circuit with specific characteristics, and is generally implemented on Field Programmable Gate Arrays (FPGAs). EHW has proven to be successful at producing small novel circuits for applications such as robot control and image processing, however, traditional approaches, in which the FPGA configuration is directly encoded on the chromosome, have not scaled well with increases in problem and FPGA architecture complexity. One of the methods proposed to overcome this is the incorporation of a growth process, known as morphogenesis, into the evolutionary process. However, existing approaches have tended to abstract away the underlying architectural details, either to present a simpler virtual FPGA architecture, or a biochemical model that hides the relationship between the cellular state and the underlying hardware. By abstracting away the underlying architectural details, EHW has moved away from one of its key strengths, that being to allow evolution to discover novel solutions free of designer bias. Also, by separating the biological model from the target FPGA architecture, too many assumptions and arbitrary decisions need to be made, which are liable to lead to the growth process failing to produce the desired results. In this thesis a new approach to applying morphogenesis to gate-level FPGA- based EHW is presented, whereby circuit growth is closely tied to the underlying gate-level architecture, with circuit growth being driven largely by the state of gate-level resources of the FPGA. An investigation into the applicability of biological processes, structures and mechanisms to morphogenetic EHW (MGEHW) is conducted, and the resulting design elaborated. The developed MGEHW system is applied to solving a signal routing problem with irregular and severe constraints on routing resources. It is shown that the morphogenetic approach outperforms a traditional EHW approach using a direct encoding, and importantly, is able to scale to larger, more complex, signal routing problems without any significant increase in the number of generations required to find an optimal solution. With the success of the MGEHW system in solving primarily structural prob- lems, it is then applied to solving a combinatorial function problem, specifically a one-bit full adder, with a more complete set of FPGA resources. The results of these experiments, together with the previous experiments, has provided valuable information that when analysed has enabled the identification of the critical factors that determine the likelihood of an EHW problem being solvable. In particular this has highlighted the importance of effective fitness feedback for guiding evolution towards its desired goal. Results indicate that the gate-level morphogenetic approach is promising. The research presented here is far from complete; many avenues for future research have opened. The MGEHW system that has been developed allows further research in this area to be explored experimentally. Some of the most fruitful directions for future research are described.

To date, studies into sex determination and gonadal development have focused on the regulatory mechanisms governing development of the male or female phenotype. However, the formation of the testis and ovary from the bipotential gonad also present a fascinating model of tissue organisation which has been largely overlooked. When seeking to understand tissue organisation during gonadal development, the formation of testis cords takes center stage. However, despite a growing understanding of the cellular events in testis development, a number of key questions about the formation of testis cords remain unanswered. Specifically, I aimed to investigate the role of cell migration in testis organization, and the structure and morphogenesis of testis cords in three dimensions. To address these aims experimentally, I investigated the early morphogenesis of testis cords and the dependence of cord formation on cell migration from the mesonephros. I found that virtually all of the migrating cells express endothelial markers, indicating that endothelial, not peritubular myoid cells underlie the dependence of cord formation on cell migration. Further, disruption of endothelial cell migration and vascular organisation using a blocking antibody to VE-cadherin, also disrupted the development of testis cords. These data reveal that migrating endothelial cells are required for testis cord formation, consistent with increasing evidence of a broader role for vasculature in establishing tissue architecture during organogenesis. To address the question of cord structure and morphogenesis, I developed and applied a novel fluorescence-based three-dimensional modeling approach to show that Sertoli cells coalesce into irregular groups surrounding germ cells, and that these groups are remodeled to form highly regular toroidal loops, joined by a flattened plexus at the dorsal side. This plexus is punctured by blood vessels as they ingress from the mesonephros, and contracts during maturation to form part of the rete testis. Variation in cord number and position demonstrates that cord establishment is not a stereotypic process. However, a tightly regulated modeling mechanism must contribute to uniformity on cord diameter and orientation as these parameters remain consistent across samples of the same age. These data clarify questions of cord structure and organisation, establish that cord formation is a variable process, and demonstrate novel structural features within the network of testis cords. Finally, to investigate an in vivo model where vascularisation and cord formation may be disrupted, I analysed gonads from embryos lacking Cited2. Consistent with a previous study, I found that testis development was delayed in Cited2-/- gonads, but found that despite the reported transcriptional recovery after the delay, testis vascular and cord structure was permanently disrupted. To investigate the defects in cord formation I assayed cell migration and found that migration was not disrupted in XY gonads, or mesonephroi lacking Cited2. However, ectopic cell migration was observed in the XX gonad in a dose-dependent response to loss of functional Cited2 alleles. Correspondingly, the female pathway was initially delayed but rallied for a late recovery, implicating Sf1 in the initiation of ovarian differentiation. These data underscore the fragility of the molecular control of sex determination as absence of Cited2 in the male permanently disrupts testis morphology, whereas in the female, promoters of the male pathway are not sufficiently suppressed. From these studies I construct an integrated model of testis cord formation and conclude that testis cord formation is a novel form of tubulogenesis. This morphogenesis is unique and offers insights into cell and tissue organisation, vascular interactions in organogenesis, and mechanisms of tube formation. Further study of cord formation is likely to lead to a broader understanding of tissue morphogenesis during development.

Congenital heart disease (CHD) is the major cause of death in the first year of life, the estimated incidence being 0.5-5% of live births; therefore it is important to understand the genetic causes underlying the complex process of heart formation to help prophylaxis, diagnosis and treatment of affected patients. CHD is the commonest phenotype associated with left-right (LR) disorders. LR asymmetry is determined during embryonic development. The three major body axes ? antero-posterior, dorso-ventral and left-right ? are patterned at gastrulation. LR asymmetry is established shortly after the two other major axes are patterned. The process of LR determination can be sub-divided into four integrated steps: 1. breaking of molecular symmetry in the gastrulation organizer; 2. transfer or relay of this asymmetric information to the lateral plate mesoderm (LPM), from which most internal organs will be formed; 3. reinforcement and propagation of asymmetric cues throughout the LPM and 4. conversion of asymmetric molecular information into proper organ morphogenesis. The goal of this work is to investigate mechanisms involved at two specific points in the laterality pathway: the initial generation/maintenance of asymmetric gene expression in the LPM and the morphogenetic translation of these early events into correct heart formation in the mouse. My emphasis has been on the characterization of laterality targeted cells via careful analysis of Pitx2c expression using a Pitx2c-lacZ reporter transgene, the role of BMP signalling, via Smad1, in generation/maintenance of early asymmetric signalling in the LPM, and the later involvement of both Smad1 and Pitx2 in cardiac morphogenesis through analyses of knockout mice.

Bibliography: p. 69-81. / 81, [52] p., [16] leaves of plates : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / This thesis demonstrates that string (a homologue of the mitotic initiator cdc 25 from Schizosaccharomyces pombe) is a downstream target of the patterning genes, making a direct connection between patterning information and morphogenesis, which suggests that mitotic timing forms an independent and important part of morphogenesis. / Thesis (Ph.D.)--University of Adelaide, Depts. of Biochemistry and Genetics, 1997

Doctor of Philosophy / This thesis looks at social interaction from the point of view of social-institutional process. In doing so, it aims to account for i) how broader institutional processes are instantiated in local interaction, and ii) how western technologisation (in the Foucaultian sense) relates to or is instantiated in local interaction.

Shoot morphogenesis in Eucalyptus occidentalis and Metrosideros excelsa was analysed at the morphological, physiological and molecular levels to understand the regulation of phase change and the floral transition. Study of the regulation of these developmental plant processes is limited in woody species due to their long juvenile phase. Six ecotypes of E. occidentalis were grown to two predetermined architectures (free branching or single stem). Free branching plants of ecotype 13648 displayed adult shoot phenology (lanceolate leaves) earlier than single stem counterparts. In addition, changes in leaf morphology in free branching plants were accompanied with changes in leaf anatomy and gas exchange signifying that in E. occidentalis complexity of shoot architecture had a significant effect on rate of phase change. Flowering was observed in all but one ecotype irrespective of architecture demonstrating that vegetative phase change and floral transition are temporally uncoupled in this species. To understand the floral transition at the molecular level in E. occidentalis, partial homologues of the inflorescence meristem identity gene TERMINAL FLOWER1 and floral meristem identity genes LEAFY and APETALA1 were isolated. The expression patterns of these meristem identity genes during development of free branching and single stem plants were analysed by quantitative real-time PCR. Increased levels of expression of EOLFY and EOAP 1 (relative to α -TUBULIN) were displayed at more proximal nodes in free branching plants than in single stem plants. Elevated floral meristem identity gene expression levels correlated with flower initiation. Further, effects of architecture and environment on gene expression were monitored in E. occidentalis. The overriding effect of shoot architecture on the floral transition was observed under warm long day and ambient environments. Elevated levels of EOLFY and EOAP 1 were correlated with floral bud score and EOAP1 was found to be a reliable marker of floral transition in E. occidentalis. Low levels of EOTFLI expression were detected in buds irrespective of their position on the plant leading to the suggestion that this might have contributed to the precocious flowering observed in this species. In contrast to E. occidentalis, M excelsa attained adult shoot phenology (pubescent leaves) faster when grown as single stem plants than as free branching plants. It appears that growth as height is required for vegetative phase change in this species. However, floral transition occurred only once single stem plants were allowed to branch. Vegetative phase change and the transition to flowering seem to be coordinated in this species with the former being a pre-requisite for the latter.

Thesis (Ph. D.)--University of Alabama at Birmingham, 2007. / Title from first page of PDF file (viewed Oct. 31, 2007). Includes bibliographical references.

Thesis (Ph.D.)--University of Missouri-Columbia, 2007. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on March 19, 2009) Vita. Includes bibliographical references.

Thesis (Ph.D. in Molecular Biology) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 160-175). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;