RESUMEN
Reproduction is paramount to animals. For it to be successful, a coordination of social behavior, physiology, and gamete production is necessary. How are social cues perceived and how do they affect physiology and gametogenesis? While females, ranging from insects to mammals, have provided multiple insights about this coordination, its existence remains largely unknown in males. Here, by using the Drosophila male as a model, we describe a phenomenon by which the availability of potential mating partners triggers an activation state on the stem cell populations of the testis, boosting spermatogenesis. We reveal its reliance on pheromonal communication, even in the absence of mating or other interactions with females. Finally, we identify the interorgan communication signaling network responsible-muscle-secreted tumor necrosis factor alpha (TNF-α)/Eiger and neuronally secreted octopamine trigger, respectively, the Jun N-terminal kinase (JNK) pathway and a change in calcium dynamics in the cyst stem cells. As a consequence, germ line stem cells increase their proliferation.
Asunto(s)
Proteínas de Drosophila , Drosophila melanogaster , Espermatogénesis , Células Madre , Animales , Masculino , Espermatogénesis/fisiología , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Células Madre/metabolismo , Femenino , Interacción Social , Testículo/metabolismo , Proliferación Celular , Conducta Sexual Animal/fisiología , Proteínas de la MembranaRESUMEN
Stem cell pools are dynamic and capable of reacting to insults like injury and starvation. Recent work has highlighted the key role of dedifferentiation as a conserved mechanism for replenishing stem cell pools after their loss, thereby maintaining tissue homeostasis. The testis of the fruit fly Drosophila melanogaster offers a simple but powerful system to study dedifferentiation, the process by which differentiating spermatogonia can revert their fate to become fully functional germline stem cells (GSCs). Dedifferentiated GSCs show interesting characteristics, such as being more proliferative than their wild-type sibling GSCs. To facilitate the study of the cellular and molecular mechanisms underlying the process of germline dedifferentiation in the Drosophila testis, here we describe techniques for inducing high rates of dedifferentiation and for unambiguously labeling dedifferentiated GSCs.
Asunto(s)
Proteínas de Drosophila , Testículo , Animales , Masculino , Espermatogonias , Drosophila , Drosophila melanogaster , Proteínas de Drosophila/genética , Células Madre , Diferenciación Celular , Células GerminativasRESUMEN
Aging causes stem cell dysfunction as a result of extrinsic and intrinsic changes. Decreased function of the stem cell niche is an important contributor to this dysfunction. We use the Drosophila testis to investigate what factors maintain niche cells. The testis niche comprises quiescent "hub" cells and supports two mitotic stem cell pools: germline stem cells and somatic cyst stem cells (CySCs). We identify the cell-cycle-responsive Dp/E2f1 transcription factor as a crucial non-autonomous regulator required in CySCs to maintain hub cell quiescence. Dp/E2f1 inhibits local Activin ligands through production of the Activin antagonist Follistatin (Fs). Inactivation of Dp/E2f1 or Fs in CySCs or promoting Activin receptor signaling in hub cells causes transdifferentiation of hub cells into fully functional CySCs. This Activin-dependent communication between CySCs and hub regulates the physiological decay of the niche with age and demonstrates that hub cell quiescence results from signals from surrounding stem cells.
Asunto(s)
Proteínas de Drosophila/metabolismo , Folistatina/metabolismo , Nicho de Células Madre , Factores de Transcripción/metabolismo , Activinas/metabolismo , Animales , Proliferación Celular , Transdiferenciación Celular , Proteínas de Drosophila/genética , Drosophila melanogaster , Masculino , Espermatozoides/citología , Espermatozoides/metabolismo , Espermatozoides/fisiología , Testículo/citología , Factores de Transcripción/genéticaRESUMEN
The Jun N-terminal kinase (JNK) pathway is an evolutionary conserved kinase cascade best known for its roles during stress-induced apoptosis and tumor progression. Recent findings, however, have identified new roles for this pleiotropic pathway in stem cells during regenerative responses and in cellular plasticity. Here, we provide an overview of recent findings about the new roles of JNK signaling in stem cell biology using two well-established Drosophila models: the testis and the intestine. We highlight the pathway's roles in processes such as proliferation, death, self-renewal and reprogramming, and discuss the known parallels between flies and mammals.
Asunto(s)
Drosophila/metabolismo , Homeostasis , Sistema de Señalización de MAP Quinasas , Células Madre/metabolismo , Animales , Diferenciación Celular , Proliferación Celular , Drosophila/fisiología , Femenino , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Masculino , Células Madre/fisiologíaRESUMEN
Cell competition is the elimination of one viable population of cells (the losers) by a neighboring fitter population (the winners) and was discovered by studies in the Drosophila melanogaster wing imaginal disc. Supercompetition is a process in which cells with elevated JAK/STAT signaling or increased Myc become winners and outcompete wild-type neighbors. To identify the genes that are differentially regulated in STAT supercompetitors, we purified these cells from Drosophila wing imaginal discs and performed next-generation sequencing. Their transcriptome was compared to those of control wing disc cells and Myc supercompetitors. Bioinformatics revealed that STAT and Myc supercompetitors have distinct transcriptomes with only 41 common differentially regulated genes. Furthermore, STAT supercompetitors have elevated reactive oxygen species, an anti-oxidant response and increased ecdysone signaling. Using a combination of methods, we validated 13 differentially expressed genes. These data sets will be useful resources to the community.
Asunto(s)
Drosophila/genética , Drosophila/metabolismo , Ecdisona/metabolismo , Estrés Oxidativo , Factores de Transcripción STAT/metabolismo , Transducción de Señal , Animales , Sitios de Unión , Biología Computacional/métodos , Genoma , Genómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Quinasas Janus/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Unión Proteica , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The JAK/STAT pathway is a conserved metazoan signaling system that transduces cues from extracellular cytokines into transcriptional changes in the nucleus. JAK/STAT signaling is best known for its roles in immunity. However, recent work has demonstrated that it also regulates critical homeostatic processes in germline and somatic stem cells, as well as regenerative processes in several tissues, including the gonad, intestine and appendages. Here, we provide an overview of JAK/STAT signaling in stem cells and regeneration, focusing on Drosophila and highlighting JAK/STAT pathway functions in proliferation, survival and cell competition that are conserved between Drosophila and vertebrates.
Asunto(s)
Drosophila/citología , Drosophila/fisiología , Quinasas Janus/metabolismo , Regeneración/fisiología , Factores de Transcripción STAT/metabolismo , Transducción de Señal , Células Madre/citología , Vertebrados/fisiología , Animales , Células Madre/metabolismoRESUMEN
Competitive interactions between neighboring cells require fitness comparison and local killing, but the signals regulating these processes are unknown. In this issue, Alpar et al. (2018) demonstrate that fitter cells secrete serine proteases to create a local burst of active Spätzle, triggering Toll signaling and apoptosis in less fit neighbors.
Asunto(s)
Proteínas de Drosophila , Receptores Toll-Like , Apoptosis , Serina Endopeptidasas , Transducción de SeñalRESUMEN
Exhaustion of stem cells is a hallmark of aging. In the Drosophila testis, dedifferentiated germline stem cells (GSCs) derived from spermatogonia increase during lifespan, leading to the model that dedifferentiation counteracts the decline of GSCs in aged males. To test this, we blocked dedifferentiation by mis-expressing the differentiation factor bag of marbles (bam) in spermatogonia while lineage-labeling these cells. Strikingly, blocking bam-lineage dedifferentiation under normal conditions in virgin males has no impact on the GSC pool. However, in mated males or challenging conditions, inhibiting bam-lineage dedifferentiation markedly reduces the number of GSCs and their ability to proliferate and differentiate. We find that bam-lineage derived GSCs have significantly higher proliferation rates than sibling GSCs in the same testis. We determined that Jun N-terminal kinase (JNK) activity is autonomously required for bam-lineage dedifferentiation. Overall, we show that dedifferentiation provides a mechanism to maintain the germline and ensure fertility under chronically stressful conditions.
Asunto(s)
Desdiferenciación Celular , Drosophila melanogaster/citología , Sistema de Señalización de MAP Quinasas , Espermatogonias/enzimología , Espermatogonias/patología , Células Madre/enzimología , Células Madre/patología , Estrés Fisiológico , Testículo/patología , Envejecimiento/metabolismo , Animales , Linaje de la Célula , Activación Enzimática , Masculino , Modelos Biológicos , EspermatogénesisRESUMEN
We discuss recent work about cellular reprogramming during regeneration of the imaginal discs of Drosophila. These contain various lineage blocks, compartments, which express distinct genetic programmes. It has been found that after massive damage to a compartment cells from a neighbour compartment can transgress the compartment border and contribute to its regeneration. The transgressing cells are genetically reprogrammed and acquire a new identity, a process facilitated by up regulation of the JNK pathway and transient loss of epigenetic control by the Pc-G and trx-G genes. The final acquisition of the new identity appears to be mediated by induction by neighbour cells, a phenomenon akin the Community Effect described for the specification of amphibian muscle cells.
Asunto(s)
Transdiferenciación Celular/genética , Reprogramación Celular/genética , Epigénesis Genética , Regeneración/genética , Animales , Proliferación Celular/genética , Drosophila , Discos Imaginales/crecimiento & desarrollo , Sistema de Señalización de MAP Quinasas/genética , Proteínas del Grupo Polycomb/genética , Alas de Animales/crecimiento & desarrolloRESUMEN
Animals have developed mechanisms to reconstruct lost or damaged tissues. To regenerate those tissues the cells implicated have to undergo developmental reprogramming. The imaginal discs of Drosophila are subdivided into distinct compartments, which derive from different genetic programs. This feature makes them a convenient system to study reprogramming during regeneration. We find that massive damage inflicted to the posterior or the dorsal compartment of the wing disc causes a transient breakdown of compartment boundaries, which are quickly reconstructed. The cells involved in the reconstruction often modify their original identity, visualized by changes in the expression of developmental genes like engrailed or cubitus interruptus. This reprogramming is mediated by up regulation of the JNK pathway and transient debilitation of the epigenetic control mechanism. Our results also show that the local developmental context plays a role in the acquisition of new cell identities: cells expressing engrailed induce engrailed expression in neighbor cells. DOI: http://dx.doi.org/10.7554/eLife.01831.001.
Asunto(s)
Reprogramación Celular , Drosophila/fisiología , Regeneración , Alas de Animales/fisiología , Animales , Epigénesis Genética , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Genes de Insecto , Sistema de Señalización de MAP QuinasasRESUMEN
Cells undergoing programmed cell death release signals that can trigger the death of cells at remote locations.
Asunto(s)
Apoptosis/fisiología , Factor de Necrosis Tumoral alfa/fisiología , AnimalesRESUMEN
All organisms have developed mechanisms to respond to organ or tissue damage that may appear during development or during the adult life. This process of regeneration is a major long-standing problem in Developmental Biology. We are using the Drosophila melanogaster wing imaginal disc to study the response to major damage inflicted during development. Using the Gal4/UAS/Gal80(TS) conditional system, we have induced massive cell killing by forcing activity of the pro-apoptotic gene hid in two major regions of the disc as defined by Gal4 inserts in the genes rotund (rn) and spalt (sal). The procedure ensures that at the end of a 40-48 hrs of ablation period the great majority of the cells of the original Rn or Sal domains have been eliminated. The results indicate that the damage provokes an immediate response aimed to keep the integrity of the epithelium and to repair the region under ablation. This includes an increase in cell proliferation to compensate for the cell loss and the replacement of the dead cells by others from outside of the damaged area. The response is almost contemporaneous with the damage, so that at the end of the ablation period the targeted region is already reconstructed. We find that the proliferative response is largely systemic, as the number of cells in division increases all over the disc. Furthermore, our results indicate that the Dpp and Wg pathways are not specifically involved in the regenerative response, but that activity of the JNK pathway is necessary both inside and outside the ablated domain for its reconstruction.
Asunto(s)
Drosophila melanogaster/crecimiento & desarrollo , Discos Imaginales , Alas de Animales , Animales , Proliferación Celular , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Regulación del Desarrollo de la Expresión Génica , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Discos Imaginales/crecimiento & desarrollo , Discos Imaginales/metabolismo , Sistema de Señalización de MAP Quinasas/genética , Transducción de Señal , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Alas de Animales/crecimiento & desarrollo , Alas de Animales/metabolismo , Proteína Wnt1/metabolismoRESUMEN
We have generated wing disc compartments that contain marked fast growing M+ clones surrounded by slow dividing M/+ cells. Under these conditions the interactions between fast and slow dividing cells at the clone borders frequently lead to cell competition. However, our assay suppressing apoptosis indicates that cell competition plays no major role in size control. We argue that cells within a compartment proliferate according to their genotype independently of each other and that their contribution to the final structure will depend solely on their proliferation rate. This model is supported by a computer simulation that predicts values similar to those found experimentally. Our results on the growth of M+ clones within compartments and on the expression of developmental genes like vestigial and wingless suggest the existence of a non-cell autonomous mechanism that functions at the level of the entire cell population. It measures the population size in each moment, determines the corresponding expression levels of developmental genes and establishes the time to arrest growth.
Asunto(s)
Drosophila/crecimiento & desarrollo , Discos Imaginales/fisiología , Metamorfosis Biológica , Alas de Animales/crecimiento & desarrollo , Animales , División Celular , Tamaño de la Célula , Células Clonales/fisiología , Simulación por Computador , Drosophila/genética , Modelos BiológicosRESUMEN
We report here experiments aimed at understanding the connections between cell competition and growth in the Drosophila wing disc. The principal assay has been to generate discs containing marked cells that proliferate at different rates and to study their interactions and their contribution to the final structure. It is known that single clones of fast-dividing cells within a compartment may occupy the larger part of the compartment without affecting its size. This has suggested the existence of interactions involving cell competition between fast- and slow-dividing cells directed to accommodate the contribution of each cell to the final compartment. Here we show that indeed fast-dividing cells can outcompete slow-dividing ones in their proximity. However, we argue that this elimination is of little consequence because preventing apoptosis, and therefore cell competition, in those compartments does not affect the size of the clones or the size of the compartments. Our experiments indicate that cells within a compartment proliferate autonomously at their own rate. The contribution of each cell to the compartment is exclusively determined by its division rate within the frame of a size control mechanism that stops growth once the compartment has reached the final arresting size. This is supported by a computer simulation of the contribution of individual fast clones growing within a population of slower dividing cells and without interacting with them. The values predicted by the simulation are very close to those obtained experimentally.