Pilot RNAi Screen in <i>Drosophila</i> Neural Stem Cell Lineages to Identify Novel Tumor Suppressor Genes Involved in Asymmetric Cell Division

A connection between compromised asymmetric cell division (ACD) and tumorigenesis was proven some years ago using <i>Drosophila</i> larval brain neural stem cells, called neuroblasts (NBs), as a model system. Since then, we have learned that compromised ACD does not always promote tumori...

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Autores principales:	Sandra Manzanero-Ortiz, Ana de Torres-Jurado, Rubí Hernández-Rojas, Ana Carmena
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	asymmetric cell division tumorigenesis neural stem cell <i>Ras<sup>V</sup></i><sup>12</sup> <i>scribble</i> <i>RNAi</i> screen tumor suppressor genes Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/2e733f88151a4cecbed7b93fa889109e
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spelling	oai:doaj.org-article:2e733f88151a4cecbed7b93fa889109e2021-11-11T16:48:55ZPilot RNAi Screen in <i>Drosophila</i> Neural Stem Cell Lineages to Identify Novel Tumor Suppressor Genes Involved in Asymmetric Cell Division10.3390/ijms2221113321422-00671661-6596https://doaj.org/article/2e733f88151a4cecbed7b93fa889109e2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11332https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067A connection between compromised asymmetric cell division (ACD) and tumorigenesis was proven some years ago using <i>Drosophila</i> larval brain neural stem cells, called neuroblasts (NBs), as a model system. Since then, we have learned that compromised ACD does not always promote tumorigenesis, as ACD is an extremely well-regulated process in which redundancy substantially overcomes potential ACD failures. Considering this, we have performed a pilot RNAi screen in <i>Drosophila</i> larval brain NB lineages using <i>Ras<sup>V</sup></i><sup>12</sup> <i>scribble (scrib)</i> mutant clones as a sensitized genetic background, in which ACD is affected but does not cause tumoral growth. First, as a proof of concept, we have tested known ACD regulators in this sensitized background, such as <i>lethal (2) giant larvae</i> and <i>warts.</i> Although the downregulation of these ACD modulators in NB clones does not induce tumorigenesis, their downregulation along with <i>Ras<sup>V</sup></i><sup>12</sup> <i>scrib</i> does cause tumor-like overgrowth. Based on these results, we have randomly screened 79 RNAi lines detecting 15 potential novel ACD regulators/tumor suppressor genes. We conclude that <i>Ras<sup>V</sup></i><sup>12</sup> <i>scrib</i> is a good sensitized genetic background in which to identify tumor suppressor genes involved in NB ACD, whose function could otherwise be masked by the high redundancy of the ACD process.Sandra Manzanero-OrtizAna de Torres-JuradoRubí Hernández-RojasAna CarmenaMDPI AGarticleasymmetric cell divisiontumorigenesisneural stem cell<i>Ras<sup>V</sup></i><sup>12</sup> <i>scribble</i><i>RNAi</i> screentumor suppressor genesBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11332, p 11332 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	asymmetric cell division tumorigenesis neural stem cell <i>Ras<sup>V</sup></i><sup>12</sup> <i>scribble</i> <i>RNAi</i> screen tumor suppressor genes Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	asymmetric cell division tumorigenesis neural stem cell <i>Ras<sup>V</sup></i><sup>12</sup> <i>scribble</i> <i>RNAi</i> screen tumor suppressor genes Biology (General) QH301-705.5 Chemistry QD1-999 Sandra Manzanero-Ortiz Ana de Torres-Jurado Rubí Hernández-Rojas Ana Carmena Pilot RNAi Screen in <i>Drosophila</i> Neural Stem Cell Lineages to Identify Novel Tumor Suppressor Genes Involved in Asymmetric Cell Division
description	A connection between compromised asymmetric cell division (ACD) and tumorigenesis was proven some years ago using <i>Drosophila</i> larval brain neural stem cells, called neuroblasts (NBs), as a model system. Since then, we have learned that compromised ACD does not always promote tumorigenesis, as ACD is an extremely well-regulated process in which redundancy substantially overcomes potential ACD failures. Considering this, we have performed a pilot RNAi screen in <i>Drosophila</i> larval brain NB lineages using <i>Ras<sup>V</sup></i><sup>12</sup> <i>scribble (scrib)</i> mutant clones as a sensitized genetic background, in which ACD is affected but does not cause tumoral growth. First, as a proof of concept, we have tested known ACD regulators in this sensitized background, such as <i>lethal (2) giant larvae</i> and <i>warts.</i> Although the downregulation of these ACD modulators in NB clones does not induce tumorigenesis, their downregulation along with <i>Ras<sup>V</sup></i><sup>12</sup> <i>scrib</i> does cause tumor-like overgrowth. Based on these results, we have randomly screened 79 RNAi lines detecting 15 potential novel ACD regulators/tumor suppressor genes. We conclude that <i>Ras<sup>V</sup></i><sup>12</sup> <i>scrib</i> is a good sensitized genetic background in which to identify tumor suppressor genes involved in NB ACD, whose function could otherwise be masked by the high redundancy of the ACD process.
format	article
author	Sandra Manzanero-Ortiz Ana de Torres-Jurado Rubí Hernández-Rojas Ana Carmena
author_facet	Sandra Manzanero-Ortiz Ana de Torres-Jurado Rubí Hernández-Rojas Ana Carmena
author_sort	Sandra Manzanero-Ortiz
title	Pilot RNAi Screen in <i>Drosophila</i> Neural Stem Cell Lineages to Identify Novel Tumor Suppressor Genes Involved in Asymmetric Cell Division
title_short	Pilot RNAi Screen in <i>Drosophila</i> Neural Stem Cell Lineages to Identify Novel Tumor Suppressor Genes Involved in Asymmetric Cell Division
title_full	Pilot RNAi Screen in <i>Drosophila</i> Neural Stem Cell Lineages to Identify Novel Tumor Suppressor Genes Involved in Asymmetric Cell Division
title_fullStr	Pilot RNAi Screen in <i>Drosophila</i> Neural Stem Cell Lineages to Identify Novel Tumor Suppressor Genes Involved in Asymmetric Cell Division
title_full_unstemmed	Pilot RNAi Screen in <i>Drosophila</i> Neural Stem Cell Lineages to Identify Novel Tumor Suppressor Genes Involved in Asymmetric Cell Division
title_sort	pilot rnai screen in <i>drosophila</i> neural stem cell lineages to identify novel tumor suppressor genes involved in asymmetric cell division
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/2e733f88151a4cecbed7b93fa889109e
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Pilot RNAi Screen in <i>Drosophila</i> Neural Stem Cell Lineages to Identify Novel Tumor Suppressor Genes Involved in Asymmetric Cell Division

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