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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/201104
Study and characterization of the Drosophila wg(1)-enhancer in development, regeneration and tumorigenesis
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[eng] Enhancers are the master regulators of gene expression. Genes rely on them to be differentially expressed in different tissues, developmental time points or contexts. In recent years, it has been reported that although there are enhancers specific for development, many developmental enhancers are “reused” in regeneration and tumorigenesis. One of these enhancers is wg1, the first ever allele described of wg. wg1 encodes an enhancer that has been described to participate in the development of the wing disc and its deletion induces the emergence of completely functional adult flies that only lack wings. Furthermore, recent reports have shown that wg1 is also involved in regeneration and tumorigenesis. However, a controversy exists among the authors on whether wg1 contributes to the three processes. Moreover, the lack of a proper characterization of wg1 makes it difficult to understand how wg1 may differently contribute to these different processes. Hence, the main aim of this thesis is to characterize wg1 and to understand how it performs its functions differentially in development, regeneration and tumorigenesis. In this thesis, we have identified a highly robust regulatory mechanism that ensures the specification and growth of the wing not only during normal development but also under stress conditions. We have narrowed down the long wing-specific enhancer to a 1.8-kb-long enhancer comprising two highly conserved regulatory modules that act in a redundant manner to guarantee the expression of Wingless (Wg) and the specification of the wing. In later stages, the same modules are reused in the injured tissue to trigger Wg and Wnt6 expression and allow regeneration. Besides, the same enhancer is aberrantly used in CIN-induced tumours to drive the expression of Wg and Wnt6 and drive the tumoral overgrowth. Furthermore, we have unveiled that the enhancer mediates these two activities through the use of distinct molecular mechanisms. Whereas Hedgehog, EGFR and JAK/STAT signalling regulate Wg expression in early primordia, JNK activation in injured tissues induce Wg expression to promote compensatory proliferation while driving tissue overgrowth in tumoral tissues. In addition, in the regenerative tissue, we have detected the presence of a cell population with enlarged nuclei and resistance to cell death inputs. Assessing different hallmarks of senescent we have been able to conclude that these cells are senescent and persist along the regeneration. Besides, we have shown that the establishment of the cell cycle arrest in the senescent population is independent of p53.
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GRACIA LATORRE, Elena. Study and characterization of the Drosophila wg(1)-enhancer in development, regeneration and tumorigenesis. [consulta: 15 de desembre de 2025]. [Disponible a: https://hdl.handle.net/2445/201104]