Apoptosis and loss of epithelial integrity in Drosophila embryos.
Doctoral thesis, UCL (University College London).
Apoptosis is a form of cell death that eliminates excessive or mis-specified cells by a caspase-dependent program. Although the machinery involved in the apoptotic process is relatively well understood, in many instances, the signals instructing cells to initiate this program remain poorly understood. In Drosophila crumbs mutant embryos, many cells of the epidermis fail to establish apico-basal polarity and undergo apoptosis as a result. Therefore crumbs embryos can be used as a model system to investigate how loss of epithelial integrity leads to apoptosis. As a first step, I have mapped the spatial and temporal pattern of cell death in the epidermis of crumbs embryos. A strip of 5-10 cells at the dorsal margin survive and give rise to the crumbs of cuticle that characterise the crumbs mutant phenotype at the end of embryogenesis. On the ventral and lateral sides, most cells undergo apoptosis, although the initial pattern of caspase activation has a clear segmental aspect, anticipated by the segmental expression of the proapoptotic gene reaper. Genetic evidence shows that reaper is indeed required for apoptosis in the trunk epidermis of crumbs embryos. The initial question can therefore be reduced to how does loss of cell polarity lead to activation of reaper expression. In order to address this question I obtained genome-wide expression data from crumbs mutant and wild type embryos at three key stages, 10, 11, and 12 of development (apoptosis begins at stage 11 in crumbs mutants). Among the upregulated genes, I have identified the transcriptional signature of the JNK signalling pathway. Functional tests have shown that this pathway is indeed required for the activation of reaper (and apoptosis) in the ventro-lateral epidermis of crumbs mutants. Additional work has enabled me to further characterise the links between epithelial integrity, JNK and apoptosis.
|Title:||Apoptosis and loss of epithelial integrity in Drosophila embryos|
|Additional information:||Permission for digitisation not received|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Cell and Developmental Biology|
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