HOX NETWORK · Identification of hox-regulated targets at different time points of a developmental process
6РП — Действия „Мария Кюри“
- Период
- 2006-10-01 → 2008-09-30
- Финансиране от ЕС
- 169 366 €
- Участници
- 1
- Схема
- EIF
Линиите свързват координатора с партньорите.
Накратко на български
Генът Ubx контролира развитието на крилата и балансиращите органи при плодовите мухи. Анализът помага да се разбере как Hox гените управляват различни нива от генетичния контрол върху формирането на органите в тялото.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - HOX NETWORK (Identification of Hox-regulated targets at different time points of a developmental process)
This project aimed to study how the developmental control genes known as Hox genes control the development of different organs at different positions within the body, using as a model system the wings of the fruit fly Drosophila. In flies, only the forewing develops as a wing, while the hindwing tissue develops as a highly modified balancing organ known as a haltere. This difference depends only on the expression of the Hox gene Ultrabithorax (Ubx), which modifies both the initial patterning of the wing tissue, and the final differentiation of wing and haltere cells, which differ dramatically in size and shape. Using the sophisticated genetics of Drosophila, we have developed a system that allows us to activate the Ubx gene specifically in the wing primordia at different times during development, without affecting its expression in the remainder of the fly. Using wing tissues isolated from flies treated in this way, we have analysed how all genes in the genome respond to the expression of Ubx protein before, during and after the dramatic developmental changes associated with metamorphosis. We find that Ubx activates or represses hundreds of target genes in the wing alone, with a time course which suggests that most of these changes are direct rather than indirect responses. The targets include other developmental control genes, as we would have expected from previous studies, but also many genes involved in the final development of adult structures - such as, for example, the genes encoding components of the insect external skeleton. These results confirm the hypothesis that the Hox genes regulate targets at many different levels in the hierarchy of genetic control. Perhaps the most interesting and novel aspect of our results is that in this one tissue, Ubx regulates a largely different set of targets at each of the three stages that we have examined. This aspect of Hox gene function, which has not previously been explored, must reflect the integration of Hox control, which defines aspects of spatial pattern, with the hormonal control pathways that control the onset of metamorphosis and the temporal sequence of development. Our results therefore provide the basis for future studies, which will analyse how these two critical aspects of developmental control interact to orchestrate the correct sequence of gene activity during development.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Hox genes are present in all animals with bilateral symmetry, providing a conserved mechanism to control regional differences along the body axis. However, little is known about the sets of genes that are modulated by the Hox proteins to mould morphologically distinct structures. The aim of this proposal is to analyse how the Hox proteins impinge on regulatory networks executing cell differentiation programmes. To study such a complex biological process, I will use as an experimental system the homeotic transformation of wing cells to haltere cells by the Hox protein Ultrabithorax (Ubx) in Drosophila melanogaster. By means of hybridisations to DNA microarrays, I will compare the transcriptome of control and Ubx-expressing wing discs. The sensitivity of these experiments will be enhanced by collecting additional microarray datasets from wing and haltere discs expressing an engineered form of Ubx with a potent transcriptional activation function. The way cells respond to Ubx changes several times during imaginal disc development. By employing a sophisticated expression system in Drosophila, I will identify the transcriptional targets of Ubx at different time points during larval and pupal development. All experiments will be done in duplicates, both with in vivo -processed discs and with discs cultured in vitro in the presence of the protein synthesis inhibitor cycloheximide. This will allow to distinguish between direct and indirect targets of Ubx. The biological significance of candidate targets will be verified by molecular genetic techniques and the relevant cis-regulatory regions will be retrieved by computational approaches. I will make use of this project to receive advanced training in complex genetic manipulations, whole-genome expression profiling, comparative genomics and bioinformatics. This research activity will be the foundation stone in a long-term work plan that will assist my career advancement in the field of Evolutionary Developmental Biology.
Оригинален текст от CORDIS (на английски).
Участници
- University of Cambridge · CambridgeКоординаторОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз
