RESUMO
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.
Assuntos
Proteínas de Drosophila/metabolismo , Folistatina/metabolismo , Nicho de Células-Tronco , Fatores de Transcrição/metabolismo , Ativinas/metabolismo , Animais , Proliferação de Células , Transdiferenciação Celular , Proteínas de Drosophila/genética , Drosophila melanogaster , Masculino , Espermatozoides/citologia , Espermatozoides/metabolismo , Espermatozoides/fisiologia , Testículo/citologia , Fatores de Transcrição/genéticaRESUMO
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.
Assuntos
Drosophila/metabolismo , Homeostase , Sistema de Sinalização das MAP Quinases , Células-Tronco/metabolismo , Animais , Diferenciação Celular , Proliferação de Células , Drosophila/fisiologia , Feminino , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Células-Tronco/fisiologiaRESUMO
Cells undergoing programmed cell death release signals that can trigger the death of cells at remote locations.
Assuntos
Apoptose/fisiologia , Fator de Necrose Tumoral alfa/fisiologia , AnimaisRESUMO
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.