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Survival Motor Neuron Protein Regulates Stem Cell Division, Proliferation, and Differentiation in Drosophila

Spinal muscular atrophy is a severe neurogenic disease that is caused by mutations in the human survival motor neuron 1 (SMN1) gene. SMN protein is required for the assembly of small nuclear ribonucleoproteins and a dramatic reduction of the protein leads to cell death. It is currently unknown how t...

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Detalles Bibliográficos
Autores principales: Grice, Stuart J., Liu, Ji-Long
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3072375/
https://www.ncbi.nlm.nih.gov/pubmed/21490958
http://dx.doi.org/10.1371/journal.pgen.1002030
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author Grice, Stuart J.
Liu, Ji-Long
author_facet Grice, Stuart J.
Liu, Ji-Long
author_sort Grice, Stuart J.
collection PubMed
description Spinal muscular atrophy is a severe neurogenic disease that is caused by mutations in the human survival motor neuron 1 (SMN1) gene. SMN protein is required for the assembly of small nuclear ribonucleoproteins and a dramatic reduction of the protein leads to cell death. It is currently unknown how the reduction of this ubiquitously essential protein can lead to tissue-specific abnormalities. In addition, it is still not known whether the disease is caused by developmental or degenerative defects. Using the Drosophila system, we show that SMN is enriched in postembryonic neuroblasts and forms a concentration gradient in the differentiating progeny. In addition to the developing Drosophila larval CNS, Drosophila larval and adult testes have a striking SMN gradient. When SMN is reduced in postembryonic neuroblasts using MARCM clonal analysis, cell proliferation and clone formation defects occur. These SMN mutant neuroblasts fail to correctly localise Miranda and have reduced levels of snRNAs. When SMN is removed, germline stem cells are lost more frequently. We also show that changes in SMN levels can disrupt the correct timing of cell differentiation. We conclude that highly regulated SMN levels are essential to drive timely cell proliferation and cell differentiation.
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spelling pubmed-30723752011-04-13 Survival Motor Neuron Protein Regulates Stem Cell Division, Proliferation, and Differentiation in Drosophila Grice, Stuart J. Liu, Ji-Long PLoS Genet Research Article Spinal muscular atrophy is a severe neurogenic disease that is caused by mutations in the human survival motor neuron 1 (SMN1) gene. SMN protein is required for the assembly of small nuclear ribonucleoproteins and a dramatic reduction of the protein leads to cell death. It is currently unknown how the reduction of this ubiquitously essential protein can lead to tissue-specific abnormalities. In addition, it is still not known whether the disease is caused by developmental or degenerative defects. Using the Drosophila system, we show that SMN is enriched in postembryonic neuroblasts and forms a concentration gradient in the differentiating progeny. In addition to the developing Drosophila larval CNS, Drosophila larval and adult testes have a striking SMN gradient. When SMN is reduced in postembryonic neuroblasts using MARCM clonal analysis, cell proliferation and clone formation defects occur. These SMN mutant neuroblasts fail to correctly localise Miranda and have reduced levels of snRNAs. When SMN is removed, germline stem cells are lost more frequently. We also show that changes in SMN levels can disrupt the correct timing of cell differentiation. We conclude that highly regulated SMN levels are essential to drive timely cell proliferation and cell differentiation. Public Library of Science 2011-04-07 /pmc/articles/PMC3072375/ /pubmed/21490958 http://dx.doi.org/10.1371/journal.pgen.1002030 Text en Grice, Liu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Grice, Stuart J.
Liu, Ji-Long
Survival Motor Neuron Protein Regulates Stem Cell Division, Proliferation, and Differentiation in Drosophila
title Survival Motor Neuron Protein Regulates Stem Cell Division, Proliferation, and Differentiation in Drosophila
title_full Survival Motor Neuron Protein Regulates Stem Cell Division, Proliferation, and Differentiation in Drosophila
title_fullStr Survival Motor Neuron Protein Regulates Stem Cell Division, Proliferation, and Differentiation in Drosophila
title_full_unstemmed Survival Motor Neuron Protein Regulates Stem Cell Division, Proliferation, and Differentiation in Drosophila
title_short Survival Motor Neuron Protein Regulates Stem Cell Division, Proliferation, and Differentiation in Drosophila
title_sort survival motor neuron protein regulates stem cell division, proliferation, and differentiation in drosophila
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3072375/
https://www.ncbi.nlm.nih.gov/pubmed/21490958
http://dx.doi.org/10.1371/journal.pgen.1002030
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