Publicação
Analysis of teashirt mutants affecting cell proliferation in Drosophila melanogaster
| Resumo: | Drosophila teashirt (tsh) encodes a zinc finger protein essential during Drosophila development. My PhD aimed to clarify the tsh role in cell proliferation studying tsh function in three Drosophila systems: follicle stem cells (FSC), neuroblasts and S2 cells. I found that Tsh and Hh were co-expressed in the Drosophila terminal filament and cap cells. A new tsh female sterile mutation exhibiting early oogenesis arrest allowed me to show that Tsh acts via Hh-mediated signalling pathway to control FSC proliferation; tsh overexpression mimics the hh overexpression associated phenotype. Additionally, in tsh background, the hsGal4 driven expression of tsh or hh partially rescues the abnormal proliferation phenotype allowing oogenesis progression. These results suggest that Tsh is critical to control hh expression contributing for the regulation of FSC proliferation and specification of somatic cell identity. In neuroblasts, hypomorphic tsh mutation leads to a metaphase-like arrest with highly condensed chromosomes associated with apparently normal mitotic spindles and centrosomes. Additionally, checkpoint proteins Bub1 and ROD were localised normally and CID imunodetection excluded an eventual premature sister chromatid separation. Furthermore, cyclin-A appears normally degraded, whereas cyclin-B remains detectable. Double tsh rod and tsh bub1 mutants phenotypes resemble the tsh single mutant. Finally, tsh depletion in S2 cells mimics the tsh mutant phenotype in neuroblasts. These results suggest that Tsh is critical during mitosis progression and I propose that Tsh loss maintains active the spindle checkpoint and/or unable the APC/C activity. We proposed a tsh acts through Hh signalling in cell proliferation. During oogenesis, tsh affects FSC proliferation mediating Hh expression. In neuroblasts, tsh could acts through Hh signalling, since expression of interference hedgehog, a positive mediator of Hh signal, was severely downregulated in microarrays-based analysis. |
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| Autores principais: | Pimentel, Sílvia Alexandra Barbosa Jácome, 1977- |
| Assunto: | Células estaminais Drosophila melanogaster Genética Divisão celular Mutação Teses de doutoramento - 2011 |
| Ano: | 2011 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Drosophila teashirt (tsh) encodes a zinc finger protein essential during Drosophila development. My PhD aimed to clarify the tsh role in cell proliferation studying tsh function in three Drosophila systems: follicle stem cells (FSC), neuroblasts and S2 cells. I found that Tsh and Hh were co-expressed in the Drosophila terminal filament and cap cells. A new tsh female sterile mutation exhibiting early oogenesis arrest allowed me to show that Tsh acts via Hh-mediated signalling pathway to control FSC proliferation; tsh overexpression mimics the hh overexpression associated phenotype. Additionally, in tsh background, the hsGal4 driven expression of tsh or hh partially rescues the abnormal proliferation phenotype allowing oogenesis progression. These results suggest that Tsh is critical to control hh expression contributing for the regulation of FSC proliferation and specification of somatic cell identity. In neuroblasts, hypomorphic tsh mutation leads to a metaphase-like arrest with highly condensed chromosomes associated with apparently normal mitotic spindles and centrosomes. Additionally, checkpoint proteins Bub1 and ROD were localised normally and CID imunodetection excluded an eventual premature sister chromatid separation. Furthermore, cyclin-A appears normally degraded, whereas cyclin-B remains detectable. Double tsh rod and tsh bub1 mutants phenotypes resemble the tsh single mutant. Finally, tsh depletion in S2 cells mimics the tsh mutant phenotype in neuroblasts. These results suggest that Tsh is critical during mitosis progression and I propose that Tsh loss maintains active the spindle checkpoint and/or unable the APC/C activity. We proposed a tsh acts through Hh signalling in cell proliferation. During oogenesis, tsh affects FSC proliferation mediating Hh expression. In neuroblasts, tsh could acts through Hh signalling, since expression of interference hedgehog, a positive mediator of Hh signal, was severely downregulated in microarrays-based analysis. |
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