Petrizzo, Arianna (2016) Drosophila dyskerin is cell-autonomously required for formation of the larval intestinal stem cell niche. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Lingua: English
Title: Drosophila dyskerin is cell-autonomously required for formation of the larval intestinal stem cell niche
Creators:
CreatorsEmail
Petrizzo, Ariannaarianna.petrizzo@gmail.com
Date: 30 March 2016
Institution: Università degli Studi di Napoli Federico II
Department: Medicina Molecolare e Biotecnologie Mediche
Scuola di dottorato: Medicina molecolare
Dottorato: Genetica e medicina molecolare
Ciclo di dottorato: 28
Coordinatore del Corso di dottorato:
nomeemail
Nitsch, Lucionitsch@unina.it
Tutor:
nomeemail
Furia, MariaUNSPECIFIED
Date: 30 March 2016
Uncontrolled Keywords: Dyskeratosis congenita, DKC1, Nop60b/mfl, snoRNPs H/ACA, Drosophila, stem cells, AMPs
Settori scientifico-disciplinari del MIUR: Area 05 - Scienze biologiche > BIO/18 - Genetica
Date Deposited: 13 Apr 2016 12:00
Last Modified: 03 May 2019 01:00
URI: http://www.fedoa.unina.it/id/eprint/10838

Abstract

Loss of function mutations of human DKC1 gene cause Dyskeratosis Congenita X-linked (X-DC), a multisystemic syndrome accompanied by telomerase defects, premature aging, increased cancer susceptibility and stem cell dysfunction. The protein encoded by DKC1, called dyskerin, is a pseudouridine synthase belonging to a highly evolutively conserved family. Dyskerin participates to the formation of the H/ACA snoRNP complexes involved in a variety of cellular functions, including pseudouridylation and processing of rRNAs, transcriptional control and telomere elongation. The striking evolutive conservation of snoRNP functions, coupled with a highly divergent mechanism of telomere lenghthening, makes Drosophila a suitable system in which to assess the mechanisms by which pseudouridine synthases regulate stemness maintenance. Since Drosophila midgut has recently emerged as an ideal model for the study of the molecular mechanisms underlying somatic stem cell maintenance, it provides an useful system to evaluate the effects caused by loss of function of genes involved in this process. I thus used the GAL4/UAS system to silence in vivo Nop60b/mfl, the Drosophila ortholog of DKC1, and investigate in detail the effects triggered by gene silencing on the formation of larval Adult Midgut Precursor (AMPs) cells. I found that mfl silencing totally disrupts the formation of larval imaginal islands, the typical stem niches in which AMPs are organized. MFL-depleted AMPs are strongly reduced in their number and appear dispersed into the epithelium, but they still retain the expression of stemness markers as escargot (a member of the Snail/Slug superfamily of Zinc finger proteins), Delta and Arm/

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