RESUMO
Many cell fate decisions are determined transcriptionally. Accordingly, some fate specification is prevented by Inhibitor of DNA binding (Id) proteins that interfere with DNA binding by master regulatory transcription factors. We show that the Drosophila Id protein Extra macrochaetae (Emc) also affect developmental decisions by regulating caspase activity. Emc, which prevents proneural bHLH transcription factors from specifying neural cell fate, also prevents homodimerization of another bHLH protein, Daughterless (Da), and thereby maintains expression of the Death-Associated Inhibitor of Apoptosis (diap1) gene. We found that multiple effects of emc mutations on cell growth and on eye development were all caused by reduced Diap1 levels and corresponding activation of caspases. These effects included acceleration of the morphogenetic furrow, failure of R7 photoreceptor cell specification, and delayed differentiation of non-neuronal cone cells. Within emc mutant clones, Notch signaling was elevated in the morphogenetic furrow, increasing morphogenetic furrow speed. This was associated with caspase-dependent increase in levels of Delta protein, the transmembrane ligand for Notch. Posterior to the morphogenetic furrow, elevated Delta cis-inhibited Notch signaling that was required for R7 specification and cone cell differentiation. Thus, emc mutations reveal the importance of restraining caspase activity even in non-apoptotic cells to prevent abnormal development, in the Drosophila eye through effects on Notch signaling.
RESUMO
The Drosophila Id gene extramacrochaetae (emc) is required during Drosophila eye development for proper cell fate specification within the R7 equivalence group. Without emc, R7 cells develop like R1/6 cells, and there are delays and deficits in differentiation of non-neuronal cone cells. Although emc encodes an Inhibitor of DNA-binding (Id) protein that is known to antagonize proneural bHLH protein function, no proneural gene is known for R7 or cone cell fates. These fates are also independent of daughterless (da), which encodes the ubiquitous E protein heterodimer partner of proneural bHLH proteins. We report here that the effects of emc mutations disappear in the absence of da, and are partially mimicked by forced expression of Da dimers, indicating that emc normally restrains da from interfering with R7 and cone cell specification, as occurs in emc mutants. emc, and da, regulate three known contributors to R7 fate, which are Notch signaling, Rap1, and Sevenless. R7 specification is partially restored to emc mutant cells by mutation of RapGap1, confirming that Rap1 activity, in addition to Notch activity, is a critical target of emc. These findings exemplify how mutations of an Id protein gene can affect processes that do not require any bHLH protein, by restraining Da activity within physiological bounds.
Assuntos
Proteínas de Drosophila , Olho , Mutação , Receptores Notch , Animais , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Receptores Notch/metabolismo , Olho/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Transdução de Sinais , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Drosophila/genética , Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Ligação a Telômeros/metabolismo , Proteínas de Ligação a Telômeros/genética , Ligação Proteica , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Complexo Shelterina , Proteínas RepressorasRESUMO
The Wnt family of developmental regulators were named after the Drosophila segmentation gene wingless and the murine proto-oncogene int-1. Homology between these two genes connected oncogenesis to cell-cell signals in development. I review how wingless was initially characterized, and cloned, as part of the quest to identify developmental cell-to-cell signals, based on predictions of the Positional Information Model, and on the properties of homeotic and segmentation gene mutants. The requirements and cell-nonautonomy of wingless in patterning multiple embryonic and adult structures solidified its status as a candidate signaling molecule. The physical location of wingless mutations and transcription unit defined the gene and its developmental transcription pattern. When the Drosophila homolog of int-1 was then isolated, and predicted to encode a secreted proto-oncogene homolog, it's identity to the wingless gene confirmed that a developmental cell-cell signal had been identified and connected cancer to development.
Assuntos
Proteínas de Drosophila , Camundongos , Animais , Proteína Wnt1/genética , Proteínas de Drosophila/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Drosophila/genética , Oncogenes , Regulação da Expressão Gênica no DesenvolvimentoRESUMO
Translation is a fundamental process of cellular behavior. Here, we present a protocol for measuring translation in Drosophila epithelial tissues using O-propargyl-puromycin (OPP), a puromycin derivative. We detail steps for larval dissection, OPP incorporation, fixation, OPP labeling, immunostaining, and imaging. We also provide details of quantification analysis. Significantly, OPP addition to methionine-containing media enables polypeptide labeling in living cells. Here, we study wing imaginal discs, an excellent model system for investigating growth, proliferation, pattern formation, differentiation, and cell death. For complete details on the use and execution of this protocol, please refer to Lee et al. (2018), Ji et al. (2019), and Kiparaki et al. (2022).1,2,3.
Assuntos
Drosophila , Discos Imaginais , Puromicina/análogos & derivados , Animais , Larva/metabolismo , Puromicina/farmacologiaRESUMO
Ribosomal protein (Rp) gene haploinsufficiency can result in Diamond-Blackfan Anemia (DBA), characterized by defective erythropoiesis and skeletal defects. Some mouse Rp mutations recapitulate DBA phenotypes, although others lack erythropoietic or skeletal defects. We generated a conditional knockout mouse to partially delete Rps12. Homozygous Rps12 deletion resulted in embryonic lethality. Mice inheriting the Rps12KO/+ genotype had growth and morphological defects, pancytopenia, and impaired erythropoiesis. A striking reduction in hematopoietic stem cells (HSCs) and progenitors in the bone marrow (BM) was associated with decreased ability to repopulate the blood system after competitive and non-competitive BM transplantation. Rps12KO/+ lost HSC quiescence, experienced ERK and MTOR activation, and increased global translation in HSC and progenitors. Post-natal heterozygous deletion of Rps12 in hematopoietic cells using Tal1-Cre-ERT also resulted in pancytopenia with decreased HSC numbers. However, post-natal Cre-ERT induction led to reduced translation in HSCs and progenitors, suggesting that this is the most direct consequence of Rps12 haploinsufficiency in hematopoietic cells. Thus, RpS12 has a strong requirement in HSC function, in addition to erythropoiesis.
Assuntos
Anemia de Diamond-Blackfan , Pancitopenia , Animais , Camundongos , Anemia de Diamond-Blackfan/genética , Anemia de Diamond-Blackfan/metabolismo , Eritropoese/genética , Genes Essenciais , Haploinsuficiência , Células-Tronco Hematopoéticas/metabolismo , Camundongos Knockout , Pancitopenia/genética , Pancitopenia/metabolismo , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismoRESUMO
Ribosomal proteins (Rps) are essential for viability. Genetic mutations affecting Rp genes were first discovered in Drosophila, where they represent a major class of haploinsufficient mutations. One mutant copy gives rise to the dominant "Minute" phenotype, characterized by slow growth and small, thin bristles. Wild-type (WT) and Minute cells compete in mosaics, that is, Rp+/- are preferentially lost when their neighbors are of the wild-type genotype. Many features of Rp gene haploinsufficiency (i.e. Rp+/- phenotypes) are mediated by a transcriptional program. In Drosophila, reduced translation and slow growth are under the control of Xrp1, a bZip-domain transcription factor induced in Rp mutant cells that leads ultimately to the phosphorylation of eIF2α and consequently inhibition of most translation. Rp mutant phenotypes are also mediated transcriptionally in yeast and in mammals. In mammals, the Impaired Ribosome Biogenesis Checkpoint activates p53. Recent findings link Rp mutant phenotypes to other cellular stresses, including the DNA damage response and endoplasmic reticulum stress. We suggest that cell competition results from nonautonomous inputs to stress responses, bringing decisions between adaptive and apoptotic outcomes under the influence of nearby cells. In Drosophila, cell competition eliminates aneuploid cells in which loss of chromosome leads to Rp gene haploinsufficiency. The effects of Rp gene mutations on the whole organism, in Minute flies or in humans with Diamond-Blackfan Anemia, may be inevitable consequences of pathways that are useful in eliminating individual cells from mosaics. Alternatively, apparently deleterious whole organism phenotypes might be adaptive, preventing even more detrimental outcomes. In mammals, for example, p53 activation appears to suppress oncogenic effects of Rp gene haploinsufficiency.
Assuntos
Proteínas de Drosophila , Proteínas Ribossômicas , Humanos , Animais , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Competição entre as Células , Mutação , Drosophila/genética , Drosophila/metabolismo , Mamíferos , Proteínas de Ligação a DNA/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismoRESUMO
Aneuploidy, the gain or loss of chromosomes, is the cause of birth defects and miscarriage and is almost ubiquitous in cancer cells. Mosaic aneuploidy causes cancer predisposition, as well as age-related disorders. Despite the cell-intrinsic mechanisms that prevent aneuploidy, sporadic aneuploid cells do arise in otherwise normal tissues. These aneuploid cells can differ from normal cells in the copy number of specific dose-sensitive genes, and may also experience proteotoxic stress associated with mismatched expression levels of many proteins. These differences may mark aneuploid cells for recognition and elimination. The ribosomal protein gene dose in aneuploid cells could be important because, in Drosophila, haploinsufficiency for these genes leads to elimination by the process of cell competition. Constitutive haploinsufficiency for human ribosomal protein genes causes Diamond Blackfan anemia, but it is not yet known whether ribosomal protein gene dose contributes to aneuploid cell elimination in mammals. In this Review, we discuss whether cell competition on the basis of ribosomal protein gene dose is a tumor suppressor mechanism, reducing the accumulation of aneuploid cells. We also discuss how this might relate to the tumor suppressor function of p53 and the p53-mediated elimination of aneuploid cells from murine embryos, and how cell competition defects could contribute to the cancer predisposition of Diamond Blackfan anemia.
Assuntos
Anemia de Diamond-Blackfan , Competição entre as Células , Humanos , Animais , Camundongos , Anemia de Diamond-Blackfan/genética , Proteína Supressora de Tumor p53/genética , Ribossomos , Aneuploidia , Proteínas Ribossômicas/genética , Drosophila , MamíferosRESUMO
Cell competition, the elimination of cells surrounded by more fit neighbors, is proposed to suppress tumorigenesis. Mahjong (Mahj), a ubiquitin E3 ligase substrate receptor, has been thought to mediate competition of cells mutated for lethal giant larvae (lgl), a neoplastic tumor suppressor that defines apical-basal polarity of epithelial cells. Here, we show that Drosophila cells mutated for mahjong, but not for lgl [l(2)gl], are competed because they express the bZip-domain transcription factor Xrp1, already known to eliminate cells heterozygous for ribosomal protein gene mutations (Rp/+ cells). Xrp1 expression in mahj mutant cells results in activation of JNK signaling, autophagosome accumulation, eIF2α phosphorylation and lower translation, just as in Rp/+ cells. Cells mutated for damage DNA binding-protein 1 (ddb1; pic) or cullin 4 (cul4), which encode E3 ligase partners of Mahj, also display Xrp1-dependent phenotypes, as does knockdown of proteasome subunits. Our data suggest a new model of mahj-mediated cell competition that is independent of apical-basal polarity and couples Xrp1 to protein turnover.
Assuntos
Proteínas de Drosophila , Fatores de Transcrição , Animais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Competição entre as Células , Proteínas de Ligação a DNA/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Proteínas de Transporte/metabolismo , Proteínas Culina/metabolismo , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismoRESUMO
Ribosomal Protein (Rp) gene haploinsufficiency affects translation rate, can lead to protein aggregation, and causes cell elimination by competition with wild type cells in mosaic tissues. We find that the modest changes in ribosomal subunit levels observed were insufficient for these effects, which all depended on the AT-hook, bZip domain protein Xrp1. Xrp1 reduced global translation through PERK-dependent phosphorylation of eIF2α. eIF2α phosphorylation was itself sufficient to enable cell competition of otherwise wild type cells, but through Xrp1 expression, not as the downstream effector of Xrp1. Unexpectedly, many other defects reducing ribosome biogenesis or function (depletion of TAF1B, eIF2, eIF4G, eIF6, eEF2, eEF1α1, or eIF5A), also increased eIF2α phosphorylation and enabled cell competition. This was also through the Xrp1 expression that was induced in these depletions. In the absence of Xrp1, translation differences between cells were not themselves sufficient to trigger cell competition. Xrp1 is shown here to be a sequence-specific transcription factor that regulates transposable elements as well as single-copy genes. Thus, Xrp1 is the master regulator that triggers multiple consequences of ribosomal stresses and is the key instigator of cell competition.
Assuntos
Competição entre as Células , Proteínas de Drosophila , Animais , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Fator de Iniciação 2 em Eucariotos/metabolismo , Fosforilação , Biossíntese de Proteínas , Ribossomos/metabolismo , Fatores de Transcrição/metabolismoRESUMO
In the last larval instar, uncommitted progenitor cells in the Drosophila eye primordium start to adopt individual retinal cell fates, arrest their growth and proliferation, and initiate terminal differentiation into photoreceptor neurons and other retinal cell types. To explore the regulation of these processes, we have performed mRNA-Seq studies of the larval eye and antennal primordial at multiple developmental stages. A total of 10,893 fly genes were expressed during these stages and could be adaptively clustered into gene groups, some of whose expression increases or decreases in parallel with the cessation of proliferation and onset of differentiation. Using in situ hybridization of a sample of 98 genes to verify spatial and temporal expression patterns, we estimate that 534 genes or more are transcriptionally upregulated during retinal differentiation, and 1367 or more downregulated as progenitor cells differentiate. Each group of co-expressed genes is enriched for regulatory motifs recognized by co-expressed transcription factors, suggesting that they represent coherent transcriptional regulatory programs. Using available mutant strains, we describe novel roles for the transcription factors SoxNeuro (SoxN), H6-like homeobox (Hmx), CG10253, without children (woc), Structure specific recognition protein (Ssrp), and multisex combs (mxc).
Assuntos
Olho Composto de Artrópodes/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Transcriptoma , Animais , Diferenciação Celular , Olho Composto de Artrópodes/crescimento & desenvolvimento , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMO
The growth and survival of cells within tissues can be affected by 'cell competition' between different cell clones. This phenomenon was initially recognized between wild-type cells and cells with mutations in ribosomal protein (Rp) genes in Drosophila melanogaster. However, competition also affects D. melanogaster cells with mutations in epithelial polarity genes, and wild-type cells exposed to 'super-competitor' cells with mutation in the Salvador-Warts-Hippo tumour suppressor pathway or expressing elevated levels of Myc. More recently, cell competition and super-competition were recognized in mammalian development, organ homeostasis and cancer. Genetic and cell biological studies have revealed that mechanisms underlying cell competition include the molecular recognition of 'different' cells, signalling imbalances between distinct cell populations and the mechanical consequences of differential growth rates; these mechanisms may also involve innate immune proteins, p53 and changes in translation.
Assuntos
Competição entre as Células/fisiologia , Sobrevivência Celular/fisiologia , Animais , Comunicação Celular , Humanos , Fígado/citologiaRESUMO
Reduced copy number of ribosomal protein (Rp) genes adversely affects both flies and mammals. Xrp1 encodes a reportedly Drosophila-specific AT-hook, bZIP protein responsible for many of the effects including the elimination of Rp mutant cells by competition with wild type cells. Irbp18, an evolutionarily conserved bZIP gene, heterodimerizes with Xrp1 and with another bZip protein, dATF4. We show that Irbp18 is required for the effects of Xrp1, whereas dATF4 does not share the same phenotype, indicating that Xrp1/Irbp18 is the complex active in Rp mutant cells, independently of other complexes that share Irbp18. Xrp1 and Irbp18 transcripts and proteins are upregulated in Rp mutant cells by auto-regulatory expression that depends on the Xrp1 DNA binding domains and is necessary for cell competition. We show that Xrp1 is conserved beyond Drosophila, although under positive selection for rapid evolution, and that at least one human bZip protein can similarly affect Drosophila development.
Assuntos
Competição entre as Células , Proteínas de Ligação a DNA/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/fisiologia , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Feminino , Masculino , Proteínas Nucleares/metabolismo , Alinhamento de Sequência , Fatores de Transcrição/metabolismo , Regulação para CimaRESUMO
Whereas complete loss of Rp function is generally lethal, most heterozygous Rp mutants grow more slowly and are subject to competitive loss from mosaics tissues that also contain wild type cells. The rpS12 gene has a special role in the cell competition of other Ribosomal Protein (Rp) mutant cells in Drosophila. Elimination by cell competition is promoted by higher RpS12 levels and prevented by a specific rpS12 mis-sense mutation, identifying RpS12 as a key effector of cell competition due to mutations in other Rp genes. Here we show that RpS12 is also required for other aspects of Rp mutant phenotypes, including hundreds of gene expression changes that occur in 'Minute' Rp heterozygous wing imaginal discs, overall translation rate, and the overall rate of organismal development, all through the bZip protein Xrp1 that is one of the RpS12-regulated genes. Our findings outline the regulatory response to mutations affecting essential Rp genes that controls overall translation, growth, and cell competition, and which may contribute to cancer and other diseases.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Discos Imaginais/crescimento & desenvolvimento , Biossíntese de Proteínas , Proteínas Ribossômicas/genética , Animais , Proteínas de Drosophila/genética , Drosophila melanogaster/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Discos Imaginais/metabolismo , Masculino , Mutação de Sentido Incorreto , Proteínas Ribossômicas/metabolismo , Análise de Sequência de RNARESUMO
Following publication of this article, it was brought to our attention that there was a typo in the References (reference number 43) whereby the first author's name was misspelled. The correct citation is provided below. We apologize for the inconvenience.
RESUMO
The fundamental roles for the Salvador-Warts-Hippo (SWH) pathway are widely characterized in growth regulation and organ size control. However, the function of SWH pathway is less known in cell fate determination. Here we uncover a novel role of the SWH signaling pathway in determination of cell fate during neural precursor (sensory organ precursor, SOP) development. Inactivation of the SWH pathway in SOP of the wing imaginal discs affects caspase-dependent bristle patterning in an apoptosis-independent process. Such nonapoptotic functions of caspases have been implicated in inflammation, proliferation, cellular remodeling, and cell fate determination. Our data indicate an effect on the Wingless (Wg)/Wnt pathway. Previously, caspases were proposed to cleave and activate a negative regulator of Wg/Wnt signaling, Shaggy (Sgg)/GSK3ß. Surprisingly, we found that a noncleavable form of Sgg encoded from the endogenous locus after CRISPR-Cas9 modification supported almost normal bristle patterning, indicating that Sgg might not be the main target of the caspase-dependent nonapoptotic process. Collectively, our results outline a new function of SWH signaling that crosstalks to caspase-dependent nonapoptotic signaling and Wg/Wnt signaling in neural precursor development, which might be implicated in neuronal pathogenesis.
Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Quinases/metabolismo , Transativadores/metabolismo , Proteína Wnt1/metabolismo , Animais , Animais Geneticamente Modificados , Apoptose/genética , Proteína 9 Associada à CRISPR/metabolismo , Inibidores de Caspase/metabolismo , Proteínas de Drosophila/genética , Drosophila melanogaster/enzimologia , Drosophila melanogaster/genética , Quinase 3 da Glicogênio Sintase/genética , Quinase 3 da Glicogênio Sintase/metabolismo , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Larva/enzimologia , Larva/genética , Larva/crescimento & desenvolvimento , Larva/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas Nucleares/genética , Organogênese/genética , Proteínas Quinases/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transdução de Sinais/genética , Transativadores/genética , Asas de Animais/enzimologia , Asas de Animais/crescimento & desenvolvimento , Asas de Animais/metabolismo , Via de Sinalização Wnt/genética , Proteína Wnt1/genética , Proteínas de Sinalização YAPRESUMO
Regulation of the Drosophila ID protein Extra macrochaetae (Emc) is important because reduced Emc levels have been proposed to favor proneural gene activity and thereby define a prepattern for neurogenesis. Recent studies suggest a major role for post-translational control of Emc levels. To further define the mechanisms of Emc regulation, we identified two redundant cis-regulatory regions by germline transformation-rescue experiments that make use of new molecularly-defined emc mutants. We distinguished the mechanisms by which Daughterless (Da) regulated Emc expression, finding post-translational regulation in most tissues, and additional transcriptional regulation in the eye imaginal disc posterior to the morphogenetic furrow. Dpp and Hh signaling pathways repressed Emc transcriptionally and post-translationally within the morphogenetic furrow of the eye disc, whereas Wg signaling repressed Emc expression at the anterior margin of the wing imaginal disc. Although the emc 3' UTR is potentially regulatory, no effect of miRNA pathways on Emc protein levels was discernible. Our work supports recent evidence that post-transcriptional mechanisms contribute more to regulation of Emc protein levels than transcriptional mechanisms do.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/genética , Regulação da Expressão Gênica no Desenvolvimento , Neurogênese/genética , Proteínas Repressoras/genética , Transcrição Gênica , Alelos , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proteínas de Drosophila/metabolismo , Loci Gênicos , MicroRNAs/genética , MicroRNAs/metabolismo , Mutação/genética , Proteínas Repressoras/metabolismo , Transdução de SinaisRESUMO
The term cell competition has been used to describe the phenomenon whereby particular cells can be eliminated during tissue growth only when more competitive cells are available to replace them. Multiple examples implicate differential activity of p53 in cell competition in mammals, but p53 has not been found to have the same role in Drosophila, where the phenomenon of cell competition was first recognized. Recent studies now show that Drosophila cells harboring mutations in Ribosomal protein (Rp) genes, which are eliminated by cell competition with wild type cells, activate a p53 target gene, Xrp1. In Diamond Blackfan Anemia, human Rp mutants activate p53 itself, through a nucleolar stress pathway. These results suggest a link between mammalian and Drosophila Rp mutants, translation, and cell competition.
Assuntos
Comunicação Celular , Proteínas de Drosophila/metabolismo , Proteínas Ribossômicas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Anemia de Diamond-Blackfan/genética , Anemia de Diamond-Blackfan/metabolismo , Animais , Sobrevivência Celular , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Modelos Animais de Doenças , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Humanos , Mutação , Proteínas Ribossômicas/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
Tumor cells often differ genetically from normal cells and from one another. Competitive interactions can occur between genetically-distinct cells, and recent studies highlight multiple examples where cell competition initiates using distinct pathways.