ArticleMolecular biology of the cell2012
Retinal horizontal cells lacking Rb1 sustain persistent DNA damage and survive as polyploid giant cells.
Article in Molecular biology of the cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Article
- Inhibition of high level E2F in a RB1 proficient MYCN overexpressing chicken retinoblastoma model normalizes neoplastic behaviour.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- MYCN induces cell-specific tumorigenic growth in RB1-proficient human retinal organoid and chicken retina models of retinoblastoma.Oncogenesis · 2022Article
- Polyploidy in the adulteLife · 2020Article
- Horizontal Cells, the Odd Ones Out in the Retina, Give Insights into Development and Disease.Frontiers in neuroanatomy · 2016Review
- p27(Kip1) participates in the regulation of endoreplication in differentiating chick retinal ganglion cells.Cell cycle (Georgetown, Tex.) · 2015Article
- Neuronal cell cycle: the neuron itself and its circumstances.Cell cycle (Georgetown, Tex.) · 2015Review
- The heterogenic final cell cycle of chicken retinal Lim1 horizontal cells is not regulated by the DNA damage response pathway.Cell cycle (Georgetown, Tex.) · 2014Article
- The terminal basal mitosis of chicken retinal Lim1 horizontal cells is not sensitive to cisplatin-induced cell cycle arrest.Cell cycle (Georgetown, Tex.) · 2014Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The retinoblastoma tumor susceptibility gene, Rb1, is a key regulator of the cell cycle, and mutations in this gene have been found in many human cancers. Prior studies showed that retina-specific knockout of Rb1 in the mouse results in the formation of abnormally large horizontal cells, but the development, fate, and genomic status of these cells remain unknown. In this study, we conditionally inactivate Rb1 in early retinal progenitors and show that the loss of Rb1 leads to the rapid degeneration of most retinal cells except horizontal cells, which persist as giant cells with aberrant centrosome content, DNA damage, and polyploidy/aneuploidy. We observed inappropriate cell cycle entry of Rb1-deficient horizontal cells during the first postnatal weeks, which dropped off abruptly by P30. Despite extensive DNA damage in Rb1-deficient horizontal cells, these cells can still enter mitosis. Adult Rb1-deficient horizontal cells display elevated DNA content (5N-34N) that varied continuously, suggesting the presence of aneuploidy. We also found evidence of supernumerary and disoriented centrosomes in a rare population of mitotic cells in the mutant retinas. Overall our data demonstrate that horizontal cells are a remarkably robust cell type and can survive for months despite extensive DNA damage and elevated genome content.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.