Mechanisms of epithelial homeostasis in adult Drosophila midgut

Stem cells confer to adult tissues the capacity to maintain morphology and function counterbalancing intrinsic wear and tear (homeostasis) and environmental damages (regeneration). Stem cells are undifferentiated multipotent cells that perpetuate themselves indefinitely. To sustain cell demand from...

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Detalles Bibliográficos
Autor: Antonello, Zeus Andrea
Tipo de recurso: tesis doctoral
Fecha de publicación:2014
País:España
Institución:Universidad Miguel Hernández de Elche
Repositorio:REDIUMH. Depósito Digital de la UMH
OAI Identifier:oai:dspace.umh.es:11000/3786
Acceso en línea:http://hdl.handle.net/11000/3786
Access Level:acceso abierto
Palabra clave:Células madre
Homeostasis
CDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncología::616.8 - Neurología. Neuropatología. Sistema nervioso
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spelling Mechanisms of epithelial homeostasis in adult Drosophila midgutAntonello, Zeus AndreaCélulas madreHomeostasisCDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncología::616.8 - Neurología. Neuropatología. Sistema nerviosoStem cells confer to adult tissues the capacity to maintain morphology and function counterbalancing intrinsic wear and tear (homeostasis) and environmental damages (regeneration). Stem cells are undifferentiated multipotent cells that perpetuate themselves indefinitely. To sustain cell demand from the tissue, they generate progenitors which are able to differentiate to substitute old and/or damaged cells. In the process of cell replacement, feedback mechanisms from the tissue to stem cells ensure adequate proliferation rate and exact lineage specification. Unfortunately, cell turnover is difficult to monitor and regeneration paradigms have been widely used to infer molecular mechanisms behind homeostatic cell turnover. But actually, very little is known about how mechanisms of regeneration resemble or differ from homeostatic tissue maintenance. In this work, using Drosophila midgut as a model, we investigated directly the basic mechanisms of epithelial homeostasis, in unchallenged conditions. To this end, we devised an original method which allowed detecting tissue turnover in a precise and temporally controllable manner in midguts. We found that in normal homeostatic conditions, midgut turnover follows unexpected asynchronous dynamics and that, surprisingly, progenitor cells sense where exactly to differentiate independently of birth time. We have identified Escargot, a Snail family gene, and the miR-200-related microRNA miR-8, as key intrinsic elements controlling this progenitor behavior during homeostasis. The escargot gene hold progenitors in undifferentiated state repressing mir-8 locus and conferring them marked mesenchymal traits that we found to be a prerequisite for proper intercalation into the epithelium. Conversely, miR-8 controls through direct targeting of escargot mRNA, the transition from undifferentiated toward differentiated state by repressing mesenchymal characteristics. The break of this reciprocal regulation impacts on homeostasis by altering the spatial and timing control of progenitors differentiation. Altogether, these results indicated that progenitors are not simple transient and passive entities but active players in homeostasis. Possibly, progenitors are able to integrate local feed-back signals to regulate their cellular state via the antagonic Escargot/miR-8 action. Given the striking analogies between Escargot/miR-8 "undifferentiated to differentiated transition" and the Snail/miR-200 mesenchymal to epithelial transition (MET), we think the future identification of the signals and molecular mechanisms controlling Escargot and miR-8 would be of wide-ranging relevance to understand not only homeostasis but also physiological and pathological related MET, as wound healing and metastasis establishment.Domínguez Castellano, MaríaInstituto de Neurociencias2017201720142017info:eu-repo/semantics/doctoralThesisapplication/pdf184application/pdfhttp://hdl.handle.net/11000/3786reponame:REDIUMH. Depósito Digital de la UMHinstname:Universidad Miguel Hernández de ElcheInglésinfo:eu-repo/semantics/openAccessoai:dspace.umh.es:11000/37862026-05-27T13:36:21Z
dc.title.none.fl_str_mv Mechanisms of epithelial homeostasis in adult Drosophila midgut
title Mechanisms of epithelial homeostasis in adult Drosophila midgut
spellingShingle Mechanisms of epithelial homeostasis in adult Drosophila midgut
Antonello, Zeus Andrea
Células madre
Homeostasis
CDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncología::616.8 - Neurología. Neuropatología. Sistema nervioso
title_short Mechanisms of epithelial homeostasis in adult Drosophila midgut
title_full Mechanisms of epithelial homeostasis in adult Drosophila midgut
title_fullStr Mechanisms of epithelial homeostasis in adult Drosophila midgut
title_full_unstemmed Mechanisms of epithelial homeostasis in adult Drosophila midgut
title_sort Mechanisms of epithelial homeostasis in adult Drosophila midgut
dc.creator.none.fl_str_mv Antonello, Zeus Andrea
author Antonello, Zeus Andrea
author_facet Antonello, Zeus Andrea
author_role author
dc.contributor.none.fl_str_mv Domínguez Castellano, María
Instituto de Neurociencias
dc.subject.none.fl_str_mv Células madre
Homeostasis
CDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncología::616.8 - Neurología. Neuropatología. Sistema nervioso
topic Células madre
Homeostasis
CDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncología::616.8 - Neurología. Neuropatología. Sistema nervioso
description Stem cells confer to adult tissues the capacity to maintain morphology and function counterbalancing intrinsic wear and tear (homeostasis) and environmental damages (regeneration). Stem cells are undifferentiated multipotent cells that perpetuate themselves indefinitely. To sustain cell demand from the tissue, they generate progenitors which are able to differentiate to substitute old and/or damaged cells. In the process of cell replacement, feedback mechanisms from the tissue to stem cells ensure adequate proliferation rate and exact lineage specification. Unfortunately, cell turnover is difficult to monitor and regeneration paradigms have been widely used to infer molecular mechanisms behind homeostatic cell turnover. But actually, very little is known about how mechanisms of regeneration resemble or differ from homeostatic tissue maintenance. In this work, using Drosophila midgut as a model, we investigated directly the basic mechanisms of epithelial homeostasis, in unchallenged conditions. To this end, we devised an original method which allowed detecting tissue turnover in a precise and temporally controllable manner in midguts. We found that in normal homeostatic conditions, midgut turnover follows unexpected asynchronous dynamics and that, surprisingly, progenitor cells sense where exactly to differentiate independently of birth time. We have identified Escargot, a Snail family gene, and the miR-200-related microRNA miR-8, as key intrinsic elements controlling this progenitor behavior during homeostasis. The escargot gene hold progenitors in undifferentiated state repressing mir-8 locus and conferring them marked mesenchymal traits that we found to be a prerequisite for proper intercalation into the epithelium. Conversely, miR-8 controls through direct targeting of escargot mRNA, the transition from undifferentiated toward differentiated state by repressing mesenchymal characteristics. The break of this reciprocal regulation impacts on homeostasis by altering the spatial and timing control of progenitors differentiation. Altogether, these results indicated that progenitors are not simple transient and passive entities but active players in homeostasis. Possibly, progenitors are able to integrate local feed-back signals to regulate their cellular state via the antagonic Escargot/miR-8 action. Given the striking analogies between Escargot/miR-8 "undifferentiated to differentiated transition" and the Snail/miR-200 mesenchymal to epithelial transition (MET), we think the future identification of the signals and molecular mechanisms controlling Escargot and miR-8 would be of wide-ranging relevance to understand not only homeostasis but also physiological and pathological related MET, as wound healing and metastasis establishment.
publishDate 2014
dc.date.none.fl_str_mv 2014
2017
2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
dc.identifier.none.fl_str_mv http://hdl.handle.net/11000/3786
url http://hdl.handle.net/11000/3786
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
184
application/pdf
dc.source.none.fl_str_mv reponame:REDIUMH. Depósito Digital de la UMH
instname:Universidad Miguel Hernández de Elche
instname_str Universidad Miguel Hernández de Elche
reponame_str REDIUMH. Depósito Digital de la UMH
collection REDIUMH. Depósito Digital de la UMH
repository.name.fl_str_mv
repository.mail.fl_str_mv
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