Thesis (Ph.D.) -- University of Adelaide, Dept. of Genetics, 2000? / Bibliography: p. 75-84.

Thesis (Ph.D.)--University of Nebraska-Lincoln, 2009. / Title from title screen (site viewed January 12, 2010). PDF text: v, 131 p. : ill. ; 3 Mb. UMI publication number: AAT 3360086. Includes bibliographical references. Also available in microfilm and microfiche formats.

There has recently been renewed interest concerning the location of the major loci responsible for the Segregation Distortion phenomenon in Drosophila melanogaster. Hartl (1974) has shown that two major sites are involved: Sd and Rsp. Rsp confers insensitivity to SD chromosomes, while Sd is considered to be the major locus that initiates distortion, Sd is located to the left of Rsp and both are located between Tft and cn. Ganetzky (1977) has extended these findings by showing that just distal to pr there is a locus that, if deleted on a SD chromosome, eliminates distortion and he argues that this is the Sd site. Ganetzky (1977) also uncovered another important locus, in or near the heterochromatin of 2L, that, if deleted from a SD chromosome, greatly reduces the ability of that chromosome to distort and he argued that this site is an enhancer of SD, E(SD). Ganetzky (1977) , also suggests that Rsp might be located very close to the centromere in the proximal heterochromatin of 2R. The results presented here demonstrate the presence of an important component of SD located within the proximal heterochromatin of 2L. These results also show that there is another important site located just distal to pr. However, when this site is removed by recombination from a SD chromosome, a certain level of residual distortion remains. It is argued that the site that Ganetzky (1977) called E(SD) is likely responsible for this residual distortion in the absence of the site just distal to pr. Thus the site near pr is called Sd₁ and the site near 1t is called Sd₂,. Loss of either site results in a large reduction, but not complete elimination, of the distorting ability of a SD chromosome. Other data are presented that, on the whole, agree with Ganetzky's (1977) proposal that Rsp is located in the centromeric heterochromatin of 2R, very close to the centromere. Miklos and Smith-White (1971) have suggested that k (the segregation ratio observed from a given mating) is a deceptive measure of the degree of distortion and they have proposed another method of measuring distortion based on their model of sperm dysfunction. Some of the weak assumptions of this model are discussed and a simpler alternative is presented. The alternative model assumes that the potential segregation ratios of a population of SD males follow a truncated normal distribution. Data are presented that are not necessarily inconsistent with this assumption. The same data show that it is likely that certain SJJ chromosomes differ in their susceptibility to modifiers of It is concluded that at present k provides the clearest measure of distortion. / Science, Faculty of / Zoology, Department of / Graduate

Includes bibliographies. / {59} leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The Polycomblike gene of Drosophila melanogaster is required for the correct spatial expression of the homeotic genes of Antenapaedia and Bithorax Complexes. This thesis describes the isolation and molecular characterization of the Polycomblike gene. / Thesis (Ph.D.)--University of Adelaide, Dept. of Biochemistry, 1995

El genoma de los híbridos interespecíficos y las especies parentales D. buzzatii y D. koepferae ha sido estudiado utilizando marcadores moleculares AFLP. En el genoma de los híbridos segregan de novo marcadores AFLP de inestabilidad que no segregan en las especies parentales, señal de que el genoma híbrido es inestable. La caracterización de los marcadores AFLP de inestabilidad ha revelado que un amplio porcentaje, que va desde el 16%, en la primera generación de híbridos, hasta un 90% en las generaciones de híbridos segmentales, está asociado a la movilización de al menos 34 elementos transponibles de clase I y II. Las tasas de transposición estimadas en los híbridos y las especies parentales para los elementos Osvaldo, Helena y Galileo confirman que hay un incremento estadísticamente significativo de la transposición del retrotransposon Osvaldo (10-2) en las tres generaciones analizadas, mientras que la tasa de transposición de Helena y Galileo se incrementa (10-2) en la generación R1 pero decrecen en la generación R3 hasta el nivel de la transposición basal de las especies parentales D. buzzatii y D. koepferae (10-3). Las inserciones de los elementos Osvaldo, Helena y Galileo observadas por FISH y por transposon display señalan que la mayor parte de las inserciones se encuentran en la heterocromatina, región en la que se encuentran silenciados. La movilización de los 34 elementos transponibles en el genoma de los híbridos evidencia que en estos genomas ocurre una reorganización genómica inducida por la movilización de los elementos transponibles, y pone de manifiesto que el estrés genómico generado por la hibridación inhibe momentáneamente los mecanismos que controlan la transposición de los ETs en el genoma híbrido, permitiendo su movilización. / The genomes of the species D. buzzatii and D. koepferae and their interspecific hybrids have been studied using AFLPs markers. In the hybrids genome markers that are absent in the parental species have been detected unveiling genome instability. High amount of AFLP instability markers, ranging from 16 % in hybrids R1 to 90 % in segmental hybrids, are related to mobilization of at least 34 transposable elements of classes I and II. Transposition rates of Osvaldo retrotransposon confirm the increase of transposition in the three generations of hybridization, however Helena and Galileo transposable elements only increase transposition in generation R1 (10-2), but show transposition rate at the basal level (10-3) in generation R3 as in parental species. Insertions of Osvaldo, Helena and Galileo observed by FISH and by the transposon display technique indicate that most of the insertions are located in the heterocromatic regions, where they are silenced. Mobilization of 34 transposable elements in the hybrid genome bolsters that a genome reorganization is occurring in the hybrids. This reorganization is probably induced when hybrid genomic stress inactivates the control mechanisms of transposable elements mobilization.

MECHANISMS OF DEPOLARIZATION INDUCED DENDRITIC GROWTH OF DROSOPHILA MOTOR NEURONS Cortnie Lauren Cherry The University of Arizona, 2006 Director: Richard B. Levine The study of the cellular mechanisms underlying dendritic growth contributes to our understanding of nervous system development, function and disease. Electrical activity is a fundamental property of neurons, and this property is utilized to influence the mechanisms involved in dendrite formation and maturation. Here we employ the Drosophila transgenic system to quantify dendritic growth of identified motor neurons using both in vitro and in vivo techniques. Two novel techniques are introduced: one a system to visualize and measure dendritic outgrowth in cultured neurons using reporter proteins, and the other using 3D reconstruction to measure the arborization of identified motor neurons in vivo. Both transgenic manipulation of K+ channel function and depolarizing concentrations of K+ in the culture medium result in an acceleration of dendritic outgrowth. Depolarization induced outgrowth is dependent on Plectreurys Toxin (PLTX)-sensitive voltage-gated calcium current and protein synthesis in cultured motor neurons. Depolarization leads to direct induction of fos, a protein that heterodimerizes with jun to make the functional transcription factor, AP-1. Fos, but not jun, is necessary for basal levels of dendritic growth, while both are necessary for depolarization induced outgrowth. Over-expression of AP-1 in control cells is sufficient to cause dendritic outgrowth. The transcription factor Adf-1 is also necessary for basal and depolarization induced growth, but unlike AP-1 is not sufficient to cause outgrowth when over-expressed. Another transcription factor CREB, on the other hand, is not necessary for basal levels of dendritic growth, but is necessary for depolarization induced dendritic growth. Over-expression of CREB, like Adf-1, is not sufficient to cause dendritic outgrowth. These findings present exciting new techniques for the study of the field of dendritic regulation and contribute to our understanding of the cellular mechanisms underlying dendritic growth.

Bibliography: p. 75-84. / 84 p., [20] leaves, [36] 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. / Identifies key interactions between Polycomblike and other members of the Polycomb group and suggests a model for the role of Polycomblike within the group. / Thesis (Ph.D.)--University of Adelaide, Dept. of Genetics, 2000?

Bibliography: p. 75-84. / 84 p., [20] leaves, [36] 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. / Identifies key interactions between Polycomblike and other members of the Polycomb group and suggests a model for the role of Polycomblike within the group. / Thesis (Ph.D.)--University of Adelaide, Dept. of Genetics, 2000?

Bibliography: p. 75-84. Identifies key interactions between Polycomblike and other members of the Polycomb group and suggests a model for the role of Polycomblike within the group.

La maladie de Huntington (MH) est une maladie neurodégénérative progressive héréditaire. Aucun traitement curatif n’a encore été trouvé. La MH est provoquée par une mutation dans le gène HTT induisant l’augmentation anormale du domaine PolyQ (>36) contenue dans la Huntingtine (Htt), la protéine codée par le gène HTT. Les conséquences et les mécanismes de cette mutation sont maintenant bien décrits et ont permis d’identifier une interaction importante entre la Htt et la voie de signalisation du BDNF. Le BDNF est un facteur neurotrophique qui joue des rôles importants, à travers l’activation de son récepteur TrkB, dans le développement et le maintien des neurones et également dans la plasticité des réseaux synaptiques. La Htt mutante (mHtt) diminue l’expression et le transport du BDNF et de TrkB dans les neurones.P42, une partie de 23 acides aminés de la Htt, est capable de sauver de nombreux phénotypes pathologiques induits dans la MH.L’objectif de ma thèse était de mieux comprendre les mécanismes d’action de P42, dans le but d’optimiser son potentiel thérapeutique. Pour cela, j’ai développé plusieurs expériences sur plusieurs modèles. Dans un article, publié dans HMG, je montre les effets d’un traitement avec P42 sur la voie de signalisation BDNF/TrkB dans un modèle de MH : les souris R6/2. Pour cela, j’ai analysé plusieurs phénotypes pathologiques, comportements et mécanismes cellulaires développés par les souris R6/2 et connus pour être dépendants de la voie BDNF/TrkB. J’ai également mesuré les taux d’ARNm et de protéine, du BDNF et de TrkB, dans le cortex et le striatum. Ce que j’ai trouvé est que P42 agit sur la voie BNDF/TrkB principalement en augmentant l’expression de TrkB dans le striatum.Afin d’observer l’effet de P42 sur le transport vésiculaire, j’ai également utilisé la drosophile comme modèle. Grâce à ce modèle, j’ai pu observer in vivo le transport vésiculaire dans différentes conditions avec ou sans mHtt ou P42.Egalement, dans le but de mieux suivre l’évolution des différents phénotypes pathologiques induits par la MH et l’effet du traitement par P42, j’ai expérimenté le Hamlet test®, un test innovant multi-comportemental.Enfin, j’ai observé sur les souris R6/2, l’effet d’une bithérapie P42 avec P3, un peptide ciblant les effets toxiques induits par les ARN codants pour un PolyQ.Tous ces résultats permettent ou vont permettre de mieux comprendre les mécanismes d’action de P42. / Huntington’s disease (HD) is a rare genetic neurodegenerative disorder. Curative treatments are still actively sought. HD is induced by a mutation in the HTT gene inducing an abnormal expansion of the polyQ domain contained in the Huntingtin protein (Htt). Mechanisms and consequences of this mutation are now well described and allowed to identify an interaction of the Htt with the brain derived neurotrophic factor (BDNF) signaling pathway. BDNF is a neurotrophic factor, which plays important roles, through TrkB, one of its receptor, in neuronal development and plasticity. Mutant Htt (mHtt) down-regulates BDNF and TrkB transcription and transport along the axons.P42, a part of the Htt protein, is a 23aa peptide able to rescue HD pathological phenotypes, such as aggregation, axonal transport and neuronal viability.The aim of my PhD was to better understand the mechanisms of action of P42, in a purpose to optimize its therapeutic potential. To this end I developed different studies using different models.In a paper now accepted for publication in HMG, I first used a P42-based treatment on R6/2 HD mice, to analyze the effect of P42 on the BDNF/TrkB signaling pathway. To this end I analyzed pathologic phenotypes: behaviors or cell mechanisms developing in R6/2 mice and are related to the BDNF/TrkB pathway. I also measured BDNF and TrkB, mRNA or protein levels in both striatum and cortex. What I found is that P42 is acting on BDNF/TrkB pathway mainly by increasing the protein level of TrkB in the striatum.To observe the effect of P42 on vesicular transport, I rather used a Drosophila model, to perform live imaging based studies, in different transgenic conditions: with or without mHTT or P42.Also, in a way to better follow the progression of different pathological phenotypes and the effect of treatments on R6/2 mice, I benefited from a very recent and innovative tool, the HAMLET, which allows a multi-behavioral test.Finally, a bitherapy was used on R6/2 mice combining P42 and P3, a peptide raised against PolyQ mRNA that are also toxic.All those results contribute or will contribute to a better understanding of P42 mechanisms of action.