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: | , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/2e733f88151a4cecbed7b93fa889109e |
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| Sumario: | 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. |
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