Clonal analysis of growth behaviors during "Drosophila" larval tracheal development.
PhD Thesis, University of Basel,
Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_8728
The discovery of the de novo formation of a tracheal structure, air sac primordium (ASP), in the second thoracic tracheal metamere (Tr2) during the 3rd instar larval stage (L3), challenged the assumption that the tracheal system established during embryogenesis would remain more or less unchanged until the onset of metamorphosis. ASP formation has since provided a novel system for studying cell behaviors such as cell migration. For ASP to form properly, it was then discovered, a process called “repopulation”, during which the composition of Tr2 changes dramatically, from the initial 20 or so cells containing bigger nuclei at early L3 to about 500 cells containing smaller nuclei at late L3, had to take place. Two models were proposed to explain how repopulation could happen. In the “replacement” model, larval tracheal cells, presumed to be terminally differentiated, endo-replicated, and incapable of dividing, would get replaced by a distinct population of mitotically active cells, the so-called “tracheoblasts”. In the “de-differentiation” model, these presumably polyploid larval tracheal cells would somehow manage to re-enter mitosis, reduce their ploidy, and produce mitotically active offspring. Using ASP morphogenesis as a model system, we performed a clonal screen to find genes important for FGF-mediated cell migration. This screen identified two major groups of genes. One group is important for cell migration, such as myosin heavy chain (mhc) and signal transducing adaptor molecule (stam); the other group is necessary for cell division. To uncover the origin of mitotic cells repopulating Tr2 during L3, we designed an in vivo clonal analysis for cell-tracking. It turned out that the “de-differentiation” model contained more grains of truth. Tr2 larval cells, possibly arrested in cell cycle prior to L3, resume cell cycle progression during L3 and give rise to mitotically competent progenies. To understand how mitotic behaviors of Tr2 cells are regulated during L3, a clonal analysis using flip-out clones was performed, which resulted in a descriptive report of the mitotic behaviors of Tr2 tracheal cells during L3. Although signals releasing Tr2 cells from cell cycle arrest and/or maintaining their proliferative state remain currently elusive, our analysis provides an assay for testing candidates likely involved. Some other interesting findings have also been revealed by this analysis, such as the existence of “regionalization” between different Tr2 branches and “cell replenishment” during ASP growth. It has gradually become clear that Drosophila tracheal system, an old model for studying tubulogenesis, proves to be a new tool for generating insights into fundamental questions such as how hox genes function, how cell cycles are developmentally controlled, how signaling pathways can be functionally dissected, and how variegated behaviors cells employ for the purpose of constructing a functional organ.
|Committee Members:||Zeller, Rolf|
|Faculties and Departments:||05 Faculty of Science > Departement Biozentrum > Growth & Development > Cell Biology (Affolter)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||130|
|Last Modified:||30 Jun 2016 10:41|
|Deposited On:||17 Jul 2009 07:03|
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