Localized JNK signaling regulates organ size during development.

A fundamental question of biology is what determines organ size. Despite demonstrations that factors within organs determine their sizes, intrinsic size control mechanisms remain elusive. Here we show that Drosophila wing size is regulated by JNK signaling during development. JNK is active in a stripe along the center of developing wings, and modulating JNK signaling within this stripe changes organ size. This JNK stripe influences proliferation in a non-canonical, Jun-independent manner by inhibiting the Hippo pathway. Localized JNK activity is established by Hedgehog signaling, where Ci elevates dTRAF1 expression. As the dTRAF1 homolog, TRAF4, is amplified in numerous cancers, these findings provide a new mechanism for how the Hedgehog pathway could contribute to tumorigenesis, and, more importantly, provides a new strategy for cancer therapies. Finally, modulation of JNK signaling centers in developing antennae and legs changes their sizes, suggesting a more generalizable role for JNK signaling in developmental organ size control

Stay in touch with the endoplasmic reticulum

The endoplasmic reticulum (ER), which is composed of a continuous network of tubules and sheets, forms the most widely distributed membrane system in eukaryotic cells. As a result, it engages a variety of organelles by establishing membrane contact sites (MCSs). These contacts regulate organelle positioning and remodeling, including fusion and fission, facilitate precise lipid exchange, and couple vital signaling events. Here, we systematically review recent advances and converging themes on ER-involved organellar contact. The molecular basis, cellular influence, and potential physiological functions for ER/nuclear envelope contacts with mitochondria, Golgi, endosomes, lysosomes, lipid droplets, autophagosomes, and plasma membrane are summarized.JH is supported by the National Natural Science Foundation of China (92254305), the Strategic Priority Research Program (XDB39000000) and Project for Young Scientists in Basic Research (YSBR-075) of the Chinese Academy of Sciences, and the National Key Research and Development Program of China (2021YFA1300800). CZ is supported by the National Natural Science Foundation of China (92254305, 91854204, 32130026). LG is supported by National Natural Science Foundation of China (92254302, 32225013, 32130023), National Key Research and Development Program of China (2021YFA0804802, 2019YFA0508602), Beijing Natural Science Foundation (JQ20028), and New Cornerstone Science Foundation (Xplorer Prize). HC is supported by grants from the National Natural Science Foundation of China (92254303, 32170701), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB37020304), and the National Key Research and Development Program of China (2021YFA1300301). GY is supported by the National Natural Science Foundation of China (91954201,31971289) and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB37040402). XH is supported by grants from the National Natural Science Foundation of China (91954207), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA24030205), and the National Key Research and Development Program of China (2018YFA0506902). YGZ is supported by the National Natural Science Foundation of China (32170753). XB is supported by the National Natural Science Foundation of China (32170692, 92154001), the Fundamental Research Funds for the Central Universities (63213104, 63223043), and the Talent Training Project at Nankai University (035-BB042112). SS is supported by grants from the National Natural Science Foundation of China (32101000, 32271273). WL is supported by the Beijing Municipal Science & Technology Commission (5202022).Peer reviewe

Tratamientos psicológicos empíricamente apoyados para adultos: Una revisión selectiva

Antecedentes: los tratamientos psicológicos han mostrado su eficacia, efectividad y eficiencia para el abordaje de los trastornos mentales; no obstante, considerando el conocimiento científico generado en los últimos años, no se dispone de trabajos de actualización en español sobre cuáles son los tratamientos psicológicos con respaldo empírico. El objetivo fue realizar una revisión selectiva de los principales tratamientos psicológicos empíricamente apoyados para el abordaje de trastornos mentales en personas adultas. Método: se recogen niveles de evidencia y grados de recomendación en función de los criterios propuestos por el Sistema Nacional de Salud de España (en las Guías de Práctica Clínica) para diferentes trastornos psicológicos. Resultados: los resultados sugieren que los tratamientos psicológicos disponen de apoyo empírico para el abordaje de un amplio elenco de trastornos psicológicos. El grado de apoyo empírico oscila de bajo a alto en función del trastorno psicológico analizado. La revisión sugiere que ciertos campos de intervención necesitan una mayor investigación. Conclusiones: a partir de esta revisión selectiva, los profesionales de la psicología podrán disponer de información rigurosa y actualizada que les permita tomar decisiones informadas a la hora de implementar aquellos procedimientos psicoterapéuticos empíricamente fundamentados en función de las características de las personas que demandan ayuda. Background: Psychological treatments have shown their efficacy, effectiveness, and efficiency in dealing with mental disorders. However, considering the scientific knowledge generated in recent years, in the Spanish context, there are no updating studies about empirically supported psychological treatments. The main goal was to carry out a selective review of the main empirically supported psychological treatments for mental disorders in adults. Method: Levels of evidence and degrees of recommendation were collected based on the criteria proposed by the Spanish National Health System (Clinical Practice Guidelines) for different psychological disorders. Results: The results indicate that psychological treatments have empirical support for the approach to a wide range of psychological disorders. These levels of empirical evidence gathered range from low to high depending on the psychological disorder analysed. The review indicates the existence of certain fields of intervention that need further investigation. Conclusions: Based on this selective review, psychology professionals will be able to have rigorous, up-to-date information that allows them to make informed decisions when implementing empirically based psychotherapeutic procedures based on the characteristics of the people who require help

Transcriptome profiling of invasive growth in imaginal disc tumor models

Resumen del trabajo presentado al Drosophila Spanish Meeting, celebrado del 14 al 16 de marzo de 2024 en Sant Joan d’Alacant (España).The sophisticated mosaic tools available in Drosophila allow the generation of genetically labeled clones of mutant cells in wild type animals. With these tools, researchers can produce tumoral models that recapitulate in flies many aspects of the biology of human cancers. For instance, when generated in the imaginal discs of the third instar larva, clones of cells expressing oncogenic RasV12 at the same time homozygous mutant for genes of the neoplastic tumor suppressor group (dlg, lgl and scrib) overgrow without control, lose cell polarity, degrade the basement membrane, metastasize to nearby and distant organs and end up killing the animal. Through the years, studies from different laboratories have revealed important determinants of the tumoral behavior of these cells, including the upregulation in them of JNK signaling, JAK/STAT cytokines, matrix metalloproteases and insulin-like peptide Dilp8. Many questions remain, however, on how tumors interact and affect the physiology of their hosts, both in the immediate vicinity of the tumor (tumorstroma interactions) and at a whole-organism level (systemic tumor effects). To better understand tumor biology, we have conducted transcriptome profiling of Drosophila eye disc tumor models, comparing the effects of RasV12 dlg, RasV12 lgl and RasV12 scrib tumors. We will present here preliminary results of this analysis.N

Mechanical coupling between dorsal and ventral surfaces shapes the Drosophila haltere

Resumen del trabajo presentado al Drosophila Spanish Meeting, celebrado del 14 al 16 de marzo de 2024 en Sant Joan d’Alacant (España).The extracellular matrix is an essential determinant of animal form, allowing organization of cells into tissues with complex 3D shapes. The Drosophila haltere, like its serial homolog the wing, is an appendage consisting of a dorsal and a ventral epithelial surface. In contrast with the dorsoventrally flat wing, the haltere presents a globular shape, thought to arise from a lack of matrix-mediated dorsoventral adhesion. Contradicting this simple model, however, matrix adhesion manipulations result in appendage deformations in both wing and haltere. To better understand the morphogenesis of the haltere, we characterized in detail matrix behavior and monitored its development during metamorphosis. We found that, similar to the wing, correct haltere morphogenesis requires Collagen IV degradation, which we show is mediated by ecdysone-controlled expression of Matrix metalloprotease 2 in both wing and haltere. After Collagen IV is degraded, similar again to the wing, the two surfaces of the haltere do not separate, but maintain laminin and integrin-mediated contact through long dorsoventral actin-microtubule projections. Furthermore, we show that these projections act as cables that mechanically couple the two surfaces of the haltere through a central tensor. Our time-lapse analysis of cell and tissue shape changes indicates that dorsoventral adhesion ensures efficient load distribution across the organ to create a 3D globular shape against cell-intrinsic and tissue-wide deforming forces. When cables are absent (loss of Laminin, Integrin or Talin) or defective (loss of microtubule-binding Shot or Sdb), mechanical coupling is lost, producing striking appendage elongation. In summary, our findings reveal an unexpected role for matrix-mediated adhesion in haltere morphogenesis and describe a novel type of matrix-based tensor structure important for building a 3D shape from 2D epithelia.N

p24-Tango1 interactions ensure ER-Golgi interface stability and efficient transport

The eukaryotic p24 family, consisting of α-, β-, γ- and δ-p24 subfamilies, has long been known to be involved in regulating secretion. Despite increasing interest in these proteins, fundamental questions remain about their role. Here, we systematically investigated Drosophila p24 proteins. We discovered that members of all four p24 subfamilies are required for general secretion and that their localizations between ER exit site (ERES) and Golgi are interdependent in an α→βδ→γ sequence. We also found that localization of p24 proteins and ERES determinant Tango1 requires interaction through their respective GOLD and SH3 lumenal domains, with Tango1 loss sending p24 proteins to the plasma membrane and vice versa. Finally, we show that p24 loss expands the COPII zone at ERES and increases the number of ER-Golgi vesicles, supporting a restrictive role of p24 proteins on vesicle budding for efficient transport. Our results reveal Tango1-p24 interplay as central to the generation of a stable ER-Golgi interface.This work was funded by grants 32150710524 and 91854207 from the National Natural Science Foundation of China and grant PID2021-122119NB-I00 from Ministerio de Ciencia e Innovación, all to J.C. Pastor-Pareja. Research by J.C. Pastor-Pareja was also funded by the “Severo Ochoa” Program for Centers of Excellence (CEX2021-001165-S).Open Access funding provided by CSIC.With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2021-001165-S).Peer reviewe

p24-Tango1 interactions ensure ER-Golgi interface stability and efficient transport

Resumen del trabajo presentado al Drosophila Spanish Meeting, celebrado del 14 al 16 de marzo de 2024 en Sant Joan d’Alacant (España).In the secretory pathway, cargos are collected at specialized ER regions called ER exit sites (ERES) prior to their transport to the Golgi apparatus. In addition to this forward secretory traffic, ERES concentrate as well the income of proteins and membranes traveling in the opposite direction from the Golgi to the ER. The question of how cells organize and maintain a dynamic but stable ER-Golgi interface in the face of constant forward and reverse traffic has sparked great interest among cell biologists. The eukaryotic p24 family, consisting of α-, β-, γ- and δ-p24 subfamilies, has long been known to be involved in regulating secretion. However, fundamental questions remain about their role. Here, we systematically investigated Drosophila p24 proteins. We discovered that members of all four p24 subfamilies are required for general secretion, and that their localizations between ERES and Golgi are interdependent in an α→βδ→γ sequence. We also found that localization of p24 proteins and ERES determinant Tango1 requires interaction through their respectiveGOLD and SH3 lumenal domains, with Tango1 loss sending p24 proteins to the plasma membrane and vice versa. Finally, we show that p24 loss expands the COPII zone at ERES and increases the number of ER-Golgi vesicles, supporting a restrictive role of p24 proteins on vesicle budding for efficient transport. Our results reveal Tango1-p24 interplay as central to the generation of a stable ER-Golgi interface.N

An innate immune response of blood cells to tumors and tissue damage in Drosophila

Studies in mice and humans have demonstrated a role for the immune system in preventing the growth of tumors. Deciphering the mechanisms involved in the immune response to tumors is essential to our understanding of immune recognition and cancer progression. Here we report an innate immune response to tumors in Drosophila melanogaster. We found that circulating blood cells, termed hemocytes, adhere to tumors upon detection of basement membrane disruption, and subsequently counter their growth. Basement membrane components are remarkably conserved throughout the animal kingdom, providing a unique structure for the immune system to sense tissue integrity. Further, we show that tissue damage activates JNK signaling in both tumors and aseptic wounds, causing expression of JAK/STAT-activating cytokines. Cytokine secretion from the injured tissue is amplified into a systemic response through the induction of additional cytokine expression in the hemocytes and the fat body, resulting in hemocyte proliferation. Our findings reveal common mechanisms in the response to tumors and wounds in flies. A similar innate reaction may underlie the response to tumors and tissue damage in vertebrates and humans

JNK signaling and integrins cooperate to maintain cell adhesion during epithelial fusion in Drosophila

The fusion of epithelial sheets is an essential and conserved morphogenetic event that requires the maintenance of tissue continuity. This is secured by membrane-bound or diffusible signals that instruct the epithelial cells, in a coordinated fashion, to change shapes and adhesive properties and when, how and where to move. Here we show that during Dorsal Closure (DC) in Drosophila, the Jun kinase (JNK) signaling pathway modulates integrins expression and ensures tissue endurance. An excess of JNK activity, as an outcome of a failure in the negative feedback implemented by the dual-specificity phosphatase Puckered (Puc), promotes the loss of integrins [the ß-subunit Myospheroid (Mys)] and amnioserosa detachment. Likewise, integrins signal back to the pathway to regulate the duration and strength of JNK activity. Mys is necessary for the regulation of JNK activity levels and in its absence, puc expression is downregulated and JNK activity increases.Peer reviewe