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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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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2011
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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. |
format | Text |
id | pubmed-3072375 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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
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title_full | Survival Motor Neuron Protein Regulates Stem Cell Division, Proliferation, and Differentiation in Drosophila
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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
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title_short | Survival Motor Neuron Protein Regulates Stem Cell Division, Proliferation, and Differentiation in Drosophila
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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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