Di Giovanni, Annamaria
(2015)
The role of the mfl/Nop60b Drosophila gene in tissue homeostasis and cell- proliferation.
[Tesi di dottorato]
| Tipologia del documento: |
Tesi di dottorato
|
| Lingua: |
English |
| Titolo: |
The role of the mfl/Nop60b Drosophila gene in tissue homeostasis and cell- proliferation |
| Autori: |
| Autore | Email |
|---|
| Di Giovanni, Annamaria | annamaria.digiovanni@unina.it |
|
| Data: |
30 Marzo 2015 |
| Numero di pagine: |
86 |
| Istituzione: |
Università degli Studi di Napoli Federico II |
| Dipartimento: |
Agraria |
| Scuola di dottorato: |
Biotecnologie |
| Dottorato: |
Insect science and biotechnology |
| Ciclo di dottorato: |
27 |
| Coordinatore del Corso di dottorato: |
| nome | email |
|---|
| Pennacchio, Francesco | f.pennacchio@unina.it |
|
| Tutor: |
| nome | email |
|---|
| Furia, Maria | [non definito] |
|
| Data: |
30 Marzo 2015 |
| Numero di pagine: |
86 |
| Parole chiave: |
Drosophila, H/ACA snoRNPs, Pseudouridine synthase, Tissue Homeostasis, Tissue Regeneration, Wg signaling, JAK/STAT pathway, JNK pathway. |
| Settori scientifico-disciplinari del MIUR: |
Area 05 - Scienze biologiche > BIO/18 - Genetica |
[error in script]
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| Depositato il: |
07 Apr 2015 09:01 |
| Ultima modifica: |
19 Mag 2018 01:00 |
| URI: |
http://www.fedoa.unina.it/id/eprint/10280 |
| DOI: |
10.6093/UNINA/FEDOA/10280 |
Abstract
The Drosophila mfl/Nop60b gene belongs to a highly conserved family whose members encode the ubiquitous pseudouridine synthase component of H/ACA snoRNPs. These nucleolar complexes are involved in essential cellular processes, such as ribosome biogenesis and RNA pseudouridylation. Loss of function mutations of the mfl/Nop60b human orthologue cause X-linked Dyskeratosis congenita, a multisystemic syndrome accompanied by telomerase defects, premature aging, stem cell dysfunction and increased cancer susceptibility. The striking conservation of snoRNP functions, coupled with a highly divergent mechanism of telomere elongation, makes Drosophila an ideal animal model in which to assess non-telomerasic functions of eukaryotic pseudouridine synthases.
Since Drosophila imaginal wing discs represent an ideal system to investigate cell death, proliferation and patterning, I focused on the effects triggered by mfl-slencing in this tissue. Here I show that localized depletion of Mfl protein in the Drosophila wing discs not only triggers apoptosis, but induces Wingless (Wg) secretion, promoting the occurrence of regenerative phenomena. I demonstrate that loss of Mfl can induce apoptosis-induced proliferation mediated by Wg and correlated with JAK/STAT pathway activation. Intriguingly, I show that Mfl depletion can also stimulate cell non- autonomous events of cell fate changes that result in Epithelial Mesenchymal Transition (EMT).
Furthermore, my experiments reveal that, upon mfl silencing, Caspase3-mediated cell death is induced by JNK activation, while mfl and jnk simultaneous silencing causes a dramatic overgrowth. These results suggest that mfl acts as a tumor suppressor and that JNK activation may represent a mechanism able to prevent the overgrowth of Mfl-depleted cells. The possibility that the interplay between pseudouridine synthase and the JNK pathway may be evolutively conserved could gain further insight into the so far unexplained high susceptibility to malignancy exhibited by X-DC patients.
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