Mutations in the Polycomb Group Gene polyhomeotic Lead to Epithelial Instability in both the Ovary and Wing Imaginal Disc in Drosophila

Most human cancers originate from epithelial tissues and cell polarity and adhesion defects can lead to metastasis. The Polycomb-Group of chromatin factors were first characterized in Drosophila as repressors of homeotic genes during development, while studies in mammals indicate a conserved role in body plan organization, as well as an implication in other processes such as stem cell maintenance, cell proliferation, and tumorigenesis. We have analyzed the function of the Drosophila Polycomb-Group gene polyhomeotic in epithelial cells of two different organs, the ovary and the wing imaginal disc.Clonal analysis of loss and gain of function of polyhomeotic resulted in segregation between mutant and wild-type cells in both the follicular and wing imaginal disc epithelia, without excessive cell proliferation. Both basal and apical expulsion of mutant cells was observed, the former characterized by specific reorganization of cell adhesion and polarity proteins, the latter by complete cytoplasmic diffusion of these proteins. Among several candidate target genes tested, only the homeotic gene Abdominal-B was a target of PH in both ovarian and wing disc cells. Although overexpression of Abdominal-B was sufficient to cause cell segregation in the wing disc, epistatic analysis indicated that the presence of Abdominal-B is not necessary for expulsion of polyhomeotic mutant epithelial cells suggesting that additional polyhomeotic targets are implicated in this phenomenon.Our results indicate that polyhomeotic mutations have a direct effect on epithelial integrity that can be uncoupled from overproliferation. We show that cells in an epithelium expressing different levels of polyhomeotic sort out indicating differential adhesive properties between the cell populations. Interestingly, we found distinct modalities between apical and basal expulsion of ph mutant cells and further studies of this phenomenon should allow parallels to be made with the modified adhesive and polarity properties of different types of epithelial tumors

Physiological apoptosis of polar cells during Drosophila oogenesis is mediated by Hid-dependent regulation of Diap1

Although much has been learned in recent years about the apoptotic machinery, the mechanisms underlying survival and death choices during development of metazoans remain less clearly understood. During early oogenesis in Drosophila, a small excess in the number of specialized somatic cells, called polar cells (PCs), produced at follicle extremities is reduced to exactly two cells through apoptosis by mid-oogenesis. We have found that PCs destined to die first lose their apical contacts and then round up and shrink progressively until they disappear. Caspases are activated only once the cells have begun to shrink, suggesting that they are implicated in this part of the process, but not in the initial loss of cell polarity. Loss-of-function analyses based on mutant, clonal and RNAi approaches show that among the RHG family of pro-apoptotic factors, Hid is specifically necessary for PC apoptosis, as well as the initiator caspase Dronc and its adaptor Dark/Apaf-1, and likely several effector caspases, in particular Drice. In addition, we show that Hid protein and transcripts accumulate specifically in PCs destined to die, while the anti-apoptotic factor Diap1 is downregulated in these cells in a hid-dependent manner. Therefore, our results implicate the Hid–Diap1 module as an important regulatory point in a developmental case of apoptosis