| Status | 已發表Published |
| C. elegans screens on polarized organ morphogenesis identify genes that regulate both polarity and growth | |
Eun, Y.; Zhang, H. ; Khan, L.; Zhang, N.; Gobel, V.
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| 2015-06-24 | |
| Source Publication | 20th International C. elegans Conference Full Abstracts
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| Abstract | In a prior RNAi-based visual tubulogenesis screen we used the polarized (apical) cytoskeleton-membrane linker ERM-1 to concomitantly identify polarity and organ morphogenesis defects in the C. elegans intestine. Among those genes whose depletion resulted in early to mid-embryonic arrest (N=619) about one third (N=264) displayed an altered subcellular localization of ERM-1. We noticed that some of these embryos also appeared to have excess intestinal cells. An association of polarity defects with hyperproliferation could support the still unconfirmed early hypothesis of cancer cell biology that a causative link exists between polarity loss and a loss of growth control. To confirm the observation and investigate this possibility, we first verified the presence of intestinal hyperproliferation in these embryos in a double transgenic strain expressing an intestinal nuclear (ELT-2::GFP) and an apical membrane (ERM-1::mCherry) marker. We rescreened the 264 genes via RNAi in this background by epifluorescence microscopy, re-evaluated genes with excess cells in a second set of RNAi experiments and confirmed the defects by confocal analysis. 28 genes (>10% of total) were identified that, when depleted, resulted in both intestinal polarity defects and excess intestinal cells. This finding could be compatible with a link between polarity establishment and growth inhibition during development, however, we are still in the process of analyzing the control group of embryonic lethal genes, whose losses did not induce appreciable polarity defects. The ability of 17/28 genes to inhibit cell/nuclear division/growth was validated by independent previous loss-of-function studies demonstrating either: multiple nuclei (5); extra intestinal cells (3); extra cell divisions in multiple tissues (3); a tumorous germline (6). Several are associated with well-defined oncogenic/tumor suppressor pathways and many of their human homologs were found to be mutated in tumors. In contrast, only few genes (4) were previously implicated in cellular asymmetries. Not all genes seem to be expressed in the intestine, suggesting the contribution of non-cell-autonomous regulation to function. This group was enriched for genes involved in microtubule dynamics and RNA regulation, as well as for genes with not-yet identified cellular functions. Experiments are underway to identify the character of a putative link between polarity and growth control and to separate early fate changes resulting in excess intestinal cells from true proliferation defects. |
| Keyword | C. elegans RNAi screens organ morphogenesis polarity and growth |
| URL | View the original |
| Language | 英語English |
| The Source to Article | PB_Publication |
| PUB ID | 14677 |
| Document Type | Conference paper |
| Collection | DEPARTMENT OF BIOMEDICAL SCIENCES Faculty of Health Sciences |
| Recommended Citation GB/T 7714 | Eun, Y.,Zhang, H.,Khan, L.,et al. C. elegans screens on polarized organ morphogenesis identify genes that regulate both polarity and growth[C], 2015. |
| APA | Eun, Y.., Zhang, H.., Khan, L.., Zhang, N.., & Gobel, V. (2015). C. elegans screens on polarized organ morphogenesis identify genes that regulate both polarity and growth. 20th International C. elegans Conference Full Abstracts. |
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