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p53 is required for brain growth but is dispensable for resistance to nutrient restriction during Drosophila larval development

BACKGROUND: Animal growth is influenced by the genetic background and the environmental circumstances. How genes promote growth and coordinate adaptation to nutrient availability is still an open question. p53 is a transcription factor that commands the cellular response to different types of stress...

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Autores principales: Contreras, Esteban G., Sierralta, Jimena, Glavic, Alvaro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5886404/
https://www.ncbi.nlm.nih.gov/pubmed/29621246
http://dx.doi.org/10.1371/journal.pone.0194344
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author Contreras, Esteban G.
Sierralta, Jimena
Glavic, Alvaro
author_facet Contreras, Esteban G.
Sierralta, Jimena
Glavic, Alvaro
author_sort Contreras, Esteban G.
collection PubMed
description BACKGROUND: Animal growth is influenced by the genetic background and the environmental circumstances. How genes promote growth and coordinate adaptation to nutrient availability is still an open question. p53 is a transcription factor that commands the cellular response to different types of stresses. In adult Drosophila melanogaster, p53 regulates the metabolic adaptation to nutrient restriction that supports fly viability. Furthermore, the larval brain is protected from nutrient restriction in a phenomenon called ‘brain sparing’. Therefore, we hypothesised that p53 may regulate brain growth and show a protective role over brain development under nutrient restriction. RESULTS: Here, we studied the function of p53 during brain growth in normal conditions and in animals subjected to developmental nutrient restriction. We showed that p53 loss of function reduced animal growth and larval brain size. Endogenous p53 was expressed in larval neural stem cells, but its levels and activity were not affected by nutritional stress. Interestingly, p53 knockdown only in neural stem cells was sufficient to decrease larval brain growth. Finally, we showed that in p53 mutant larvae under nutrient restriction, the energy storage levels were not altered, and these larvae generated adults with brains of similar size than wild-type animals. CONCLUSIONS: Using genetic approaches, we demonstrate that p53 is required for proper growth of the larval brain. This developmental role of p53 does not have an impact on animal resistance to nutritional stress since brain growth in p53 mutants under nutrient restriction is similar to control animals.
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spelling pubmed-58864042018-04-20 p53 is required for brain growth but is dispensable for resistance to nutrient restriction during Drosophila larval development Contreras, Esteban G. Sierralta, Jimena Glavic, Alvaro PLoS One Research Article BACKGROUND: Animal growth is influenced by the genetic background and the environmental circumstances. How genes promote growth and coordinate adaptation to nutrient availability is still an open question. p53 is a transcription factor that commands the cellular response to different types of stresses. In adult Drosophila melanogaster, p53 regulates the metabolic adaptation to nutrient restriction that supports fly viability. Furthermore, the larval brain is protected from nutrient restriction in a phenomenon called ‘brain sparing’. Therefore, we hypothesised that p53 may regulate brain growth and show a protective role over brain development under nutrient restriction. RESULTS: Here, we studied the function of p53 during brain growth in normal conditions and in animals subjected to developmental nutrient restriction. We showed that p53 loss of function reduced animal growth and larval brain size. Endogenous p53 was expressed in larval neural stem cells, but its levels and activity were not affected by nutritional stress. Interestingly, p53 knockdown only in neural stem cells was sufficient to decrease larval brain growth. Finally, we showed that in p53 mutant larvae under nutrient restriction, the energy storage levels were not altered, and these larvae generated adults with brains of similar size than wild-type animals. CONCLUSIONS: Using genetic approaches, we demonstrate that p53 is required for proper growth of the larval brain. This developmental role of p53 does not have an impact on animal resistance to nutritional stress since brain growth in p53 mutants under nutrient restriction is similar to control animals. Public Library of Science 2018-04-05 /pmc/articles/PMC5886404/ /pubmed/29621246 http://dx.doi.org/10.1371/journal.pone.0194344 Text en © 2018 Contreras et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Contreras, Esteban G.
Sierralta, Jimena
Glavic, Alvaro
p53 is required for brain growth but is dispensable for resistance to nutrient restriction during Drosophila larval development
title p53 is required for brain growth but is dispensable for resistance to nutrient restriction during Drosophila larval development
title_full p53 is required for brain growth but is dispensable for resistance to nutrient restriction during Drosophila larval development
title_fullStr p53 is required for brain growth but is dispensable for resistance to nutrient restriction during Drosophila larval development
title_full_unstemmed p53 is required for brain growth but is dispensable for resistance to nutrient restriction during Drosophila larval development
title_short p53 is required for brain growth but is dispensable for resistance to nutrient restriction during Drosophila larval development
title_sort p53 is required for brain growth but is dispensable for resistance to nutrient restriction during drosophila larval development
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5886404/
https://www.ncbi.nlm.nih.gov/pubmed/29621246
http://dx.doi.org/10.1371/journal.pone.0194344
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