Drosophila dyskerin is required for somatic stem cell homeostasis.
Drosophila represents an excellent model to dissect the roles played by the evolutionary conserved family of eukaryotic dyskerins. These multifunctional proteins are involved in the formation of H/ACA snoRNP and telomerase complexes, both involved in essential cellular tasks. Since fly telomere integrity is guaranteed by a different mechanism, we used this organism to investigate the specific role played by dyskerin in somatic stem cell maintenance. To this aim, we focussed on Drosophila midgut, a hierarchically organized and well characterized model for stemness analysis. Surprisingly, the ubiquitous loss of the protein uniquely affects the formation of the larval stem cell niches, without altering other midgut cell types. The number of adult midgut precursor stem cells is dramatically reduced, and this effect is not caused by premature differentiation and is cell-autonomous. Moreover, a few dispersed precursors found in the depleted midguts can maintain stem identity and the ability to divide asymmetrically, nor show cell-growth defects or undergo apoptosis. Instead, their loss is mainly specifically dependent on defective amplification. These studies establish a strict link between dyskerin and somatic stem cell maintenance in a telomerase-lacking organism, indicating that loss of stemness can be regarded as a conserved, telomerase-independent effect of dyskerin dysfunction.
Department of Biology, University of Naples "Federico II", Complesso Universitario Monte Santangelo, via Cinthia, 80126, Napoli, Italy. rosario.vicidomini@nih.gov.|NICHD (National Institute of Child Health and Human Development), Section on Metabolic Regulation - NIH- 35 Convent DR, Bethesda, MD, 20814, USA. rosario.vicidomini@nih.gov.
Rosario
R
Vicidomini
Department of Biology, University of Naples "Federico II", Complesso Universitario Monte Santangelo, via Cinthia, 80126, Napoli, Italy.
Arianna
A
Petrizzo
Department of Biology, University of Naples "Federico II", Complesso Universitario Monte Santangelo, via Cinthia, 80126, Napoli, Italy.
Annamaria
A
di Giovanni
Department of Biology, University of Naples "Federico II", Complesso Universitario Monte Santangelo, via Cinthia, 80126, Napoli, Italy.
Laura
L
Cassese
Department of Biology, University of Naples "Federico II", Complesso Universitario Monte Santangelo, via Cinthia, 80126, Napoli, Italy.
Antonella Anna
AA
Lombardi
Department of Biology, University of Naples "Federico II", Complesso Universitario Monte Santangelo, via Cinthia, 80126, Napoli, Italy.
Caterina
C
Pragliola
Department of Biology, University of Naples "Federico II", Complesso Universitario Monte Santangelo, via Cinthia, 80126, Napoli, Italy. mfuria@unina.it.
Maria
M
Furia
D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation; D004330:Drosophila / Q000254:growth & development; D029721:Drosophila Proteins / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000254:growth & development; D006706:Homeostasis; D006836:Hydro-Lyases / Q000502:physiology*; D007814:Larva / Q000254:growth & development; D009687:Nuclear Proteins / Q000502:physiology*; D016601:RNA-Binding Proteins; D055153:Stem Cell Niche
D029721:Drosophila Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D006836:Hydro-Lyases; C119240:Nop60B protein, Drosophila