Pituitary adenomas are among the most frequent intracranial neoplasms and treatment depends on tumor subtype and clinical features. Unfortunately, non responder cases occur, then new molecular targets are needed.Notch system component expression and activation data are scarce in pituitary tumorigenesis, we therefore aimed to characterize Notch system in pituitary tumors of different histotype. In human pituitary adenomas we showed NOTCH1-4 receptors, JAGGED1 ligand and HES1 target gene expression with positive correlations between NOTCH1,2,4 and HES1, and NOTCH3 and JAGGED1 denoting Notch system activation in a subset of tumors. Importantly, NOTCH3 positive cells were higher in corticotropinomas and somatotropinomas compared to non functioning adenomas. In accordance, Notch activation was evidenced in AtT20 tumor corticotropes, with higher levels of NOTCH1-3 active domains, Jagged1 and Hes1 compared to normal pituitary.In the prolactinoma cell lines GH3 and MMQ, in vivo GH3 tumors and normal glands, Notch system activation was lower than in corticotropes. In MMQ cells only the NOTCH2 active domain was increased, whereas NOTCH1 active domain was higher in GH3 tumors. High levels of Jagged1 and Dll1 were found solely in GH3 cells, and Hes1, Hey1 and Hey2 were expressed in a model dependent pattern.Prolactinomas harbored by lacDrd2KO mice expressed high levels of NOTCH1 active domain and reduced Hes1.We show a differential expression of Notch system components in tumoral and normal pituitaries and specific Notch system involvement depending on adenoma histotype, with higher activation in corticotropinomas. These data suggest that targeting Notch pathway may benefit non responder pituitary adenomas.
BACKGROUND: The corn leafhopper Dalbulus maidis is the main vector of important stunting pathogens that affect maize production. Currently, there are no effective methods available to manage this pest without adverse impact on the environment. In this context, genomic-based technologies such as RNA interference (RNAi) provide a more environmentally friendly pest control strategy. Therefore, we aimed to assess the application of RNAi in D. maidis and determine the function of a candidate gene related to insect reproduction and propagation.RESULTS: We have characterized the core RNAi genes and evaluated the functionality of the RNAi machinery. We assessed the potential of RNAi technology in D. maidis via injection or ingestion of double-stranded RNA (dsRNA) to adult females. We chose Bicaudal C (BicC) as a target gene due to its important role during insect oogenesis. Administration of dsRNA BicC caused significant reductions in the transcript levels (fold changes up to 170 times) and ovipositions. Phenotypic analysis of the ovaries revealed alterations in oocyte development, providing additional confirmation for our results and supporting the idea that Dmai-BicC is a key player of D. maidis oogenesis.CONCLUSION: This is, to our knowledge, the first report of efficient RNAi in D. maidis. We believe our findings provide a starting point for future control strategies against one of the most important maize pests in the Americas.
BACKGROUND: The corn leafhopper Dalbulus maidis is the main vector of three important stunting pathogens that affect maize production. The most common control strategy against this species is the use of insecticides that provide minimal, short-term protection. In this context, genomic-based technologies such as RNA interference (RNAi) could be a suitable approach to control this pest in a highly specific manner, avoiding the adverse effects associated with insecticide misuse. Therefore, the objective of the present work was to assess the application of RNAi on D. maidis through different dsRNA delivery methods and known the function of target gene, Bicaudal C (BicC). RESULTS: We have identified and characterized the core components of the RNAi machinery in silico and established two methods of exogenous double-stranded RNAs (dsRNA) delivery to D. maidis. BicC -an important regulator of insect oogenesis- dsRNA was successfully delivered via injection or ingestion to adult females, causing significant reductions in the transcript levels and ovipositions and observable phenotypes in the ovaries when compared to control females. The small doses of dsRNABicC administered were enough to trigger a strong RNAi response, demonstrating that D. maidis is highly sensitive to RNAi. CONCLUSION: This is, to our knowledge, the first report describing RNAi application in D. maidis, a tool that can be used to advance towards a novel, insecticide-free control strategy against this pest.
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