Integrins regulate epithelial cell shape by controlling the architecture and mechanical properties of basal actomyosin networks.

Forces generated by the actomyosin cytoskeleton are key contributors to many morphogenetic processes. The actomyosin cytoskeleton organises in different types of networks depending on intracellular signals and on cell-cell and cell-extracellular matrix (ECM) interactions. However, actomyosin networks are not static and transitions between them have been proposed to drive morphogenesis. Still, little is known about the mechanisms that regulate the dynamics of actomyosin networks during morphogenesis. This work uses the Drosophila follicular epithelium, real-time imaging, laser ablation and quantitative analysis to study the role of integrins on the regulation of basal actomyosin networks organisation and dynamics and the potential contribution of this role to cell shape. We find that elimination of integrins from follicle cells impairs F-actin recruitment to basal medial actomyosin stress fibers. The available F-actin redistributes to the so-called whip-like structures, present at tricellular junctions, and into a new type of actin-rich protrusions that emanate from the basal cortex and project towards the medial region. These F-actin protrusions are dynamic and changes in total protrusion area correlate with periodic cycles of basal myosin accumulation and constriction pulses of the cell membrane. Finally, we find that follicle cells lacking integrin function show increased membrane tension and reduced basal surface. Furthermore, the actin-rich protrusions are responsible for these phenotypes as their elimination in integrin mutant follicle cells rescues both tension and basal surface defects. We thus propose that the role of integrins as regulators of stress fibers plays a key role on controlling epithelial cell shape, as integrin disruption promotes reorganisation into other types of actomyosin networks, in a manner that interferes with proper expansion of epithelial basal surfaces

Carotenoids from persimmon juice processing

[EN] The aim of this study was the use and revalorization of two persimmon by-products A and B generated in the juice production process. The by-product B resulting from a pectinase enzymatic treatment of peels and pulp to optimize juice extraction was especially suitable for recovery of valuable bioactive carotenoids. The extraction solvents and solvent combinations used were: ethanol, acetone, ethanol/acetone (50:50 v/v) and ethanol/ acetone/hexane (25:25:50 v/v/v). HPLC-DAD analysis detected and identified a total of nine individual carotenoids namely violaxanthin, neoxanthin, antheraxanthin, lutein, zeaxanthin, ß-cryptoxanthin 5,6-epoxide, ß-cryptoxanthin, ¿-carotene, and ß-carotene. ß-cryptoxanthin and ß-carotene represented 49.2% and 13.2% of the total carotenoid content (TCC) in the acetone extract from by-product B. TCC contributed greatly to antioxidant activity of acetone extract derived from this by-product. Pectinase enzymatic treatment of persimmon peels and pulp followed by absolute acetone extraction of carotenoids could be an efficient method to obtain a rich extract in these compounds that could be used as nutraceutical ingredient.This study was supported by Ministerio de Ciencia, Innovacion y Universidades through the funded project 'Simbiosis industrial en el aprovechamiento integral del caqui (Diospyros kaki); Ejemplo de bioeconomia' (CTM2017-88978-R). Sara Gea-Botella thanks the Agencia Estatal de Investigacion la Ayuda para la Formacion de Doctores en Empresas "Doctorados Industriales" (DI-16-08465) through the R+D+i project entitled 'Evaluacion in vitro e in vivo de un extracto procedente de subproductos de la industrializacion del caqui'. The authors wish to thank Mitra Sol Technologies S.L. the given technical assistance.Gea-Botella, S.; Agulló, L.; Martí, N.; Martínez-Madrid, M.; Lizama Abad, V.; Martín-Bermudo, F.; Berná, G.... (2021). Carotenoids from persimmon juice processing. Food Research International. 141:1-8. https://doi.org/10.1016/j.foodres.2020.109882S1814

PS Integrins and Laminins: Key Regulators of Cell Migration during Drosophila Embryogenesis

During embryonic development, there are numerous cases where organ or tissue formation depends upon the migration of primordial cells. In the Drosophila embryo, the visceral mesoderm (vm) acts as a substrate for the migration of several cell populations of epithelial origin, including the endoderm, the trachea and the salivary glands. These migratory processes require both integrins and laminins. The current model is that αPS1βPS (PS1) and/or αPS3βPS (PS3) integrins are required in migrating cells, whereas αPS2βPS (PS2) integrin is required in the vm, where it performs an as yet unidentified function. Here, we show that PS1 integrins are also required for the migration over the vm of cells of mesodermal origin, the caudal visceral mesoderm (CVM). These results support a model in which PS1 might have evolved to acquire the migratory function of integrins, irrespective of the origin of the tissue. This integrin function is highly specific and its specificity resides mainly in the extracellular domain. In addition, we have identified the Laminin α1,2 trimer, as the key extracellular matrix (ECM) component regulating CVM migration. Furthermore, we show that, as it is the case in vertebrates, integrins, and specifically PS2, contributes to CVM movement by participating in the correct assembly of the ECM that serves as tracks for migration

The humble fruit fly is helping the African science community to thrive

Africa generates less than 2% of the world’s research output, while representing 15% of the global population. This limits Africa’s capacity to lead its own way towards important sustainable development goals, which requires bringing knowledge generation to the forefront to reduce disease burden and boost the economies. Africa has around 200 researchers per million people, while the UK, for example, has 4,000. The challenge is how to generate — and later retain — the million of postgraduate researchers needed to meet the world average, in a continent where governments struggle to cover their health-care programme and spend less than 1% of their GDP in research and development. In 2013, after teaching in a course in Kampala International University in the Bushenyi District of Uganda, with participants from various African institutions, we, Isabel, Maria D. (Lola) and Marta, realized that the continent is full of talented scientists who find little support to pursue their passion for active and competitive research. To work towards improving this situation, and inspired by the example of Spain, where popularization of the fruit fly as a model system during the second half of the 1900s led to a period of unprecedented growth and development of biomedical research, we founded DrosAfrica in 2013

Biophysical constraints drive three-dimensional architecture in epithelial organs

Resumen del póster presentado al 1st Joint Meeting of the French-Portuguese-Spanish Biochemical and Molecular Biology Societies y al XL Spanish Society of Biochemistry and Molecular Biology (SEBBM) Congress, celebrado en Barcelona (España) del 23 al 26 de octubre de 2017.-- et al.As animals develop, the initial simple planar epithelia of embryos must be sculpted into complex three-dimensional tissues. Epithelial bending is therefore a general principle of all developing systems. Here we use different geometrical and biophysical models to analyse three-dimensional packing in curved structures. We fi nd that under specific circumstances tissue bending induces a neighbour exchange along the apico-basal axis of epithelial cells. This causes cells participating in these crucial motifs to adopt an undescribed geometrical confi guration that we name “scutoids”. Strikingly, analyses of different curved tissues and glands confirm the apparition of scutoids during morphogenesis. Using simple geometrical and biophysical concepts we are able to predict the emergence of scutoids. We conclude that the generation of the previously unnoticed scutoids is necessary for the bending of the tissue. Our fi ndings pave the way for understanding how epithelial structures such as glands and organs are formed and maintained.Peer reviewe

Laminins are required for proper formation and maturation of eggs in Drosophila

Resumen del trabajo presentado al XXIV International Congress of Entomology, celebrado en Daegu (Kórea) del 19 al 25 de agosto de 2012.Peer Reviewe

Integrins cooperate with the EGFR/Ras pathway to preserve epithelia survival and architecture in development and oncogenesis

© 2022 Valencia-Expósito, Gómez-Lamarca, Widmann and Martín-Bermudo.Adhesion to the extracellular matrix (ECM) is required for normal epithelial cell survival. Disruption of this interaction leads to a specific type of apoptosis known as anoikis. Yet, there are physiological and pathological situations in which cells not connected to the ECM are protected from anoikis, such as during cell migration or metastasis. The main receptors transmitting signals from the ECM are members of the integrin family. However, although integrin-mediated cell-ECM anchorage has been long recognized as crucial for epithelial cell survival, the in vivo significance of this interaction remains to be weighed. In this work, we have used the Drosophila wing imaginal disc epithelium to analyze the importance of integrins as survival factors during epithelia morphogenesis. We show that reducing integrin expression in the wing disc induces caspase-dependent cell death and basal extrusion of the dead cells. In this case, anoikis is mediated by the activation of the JNK pathway, which in turn triggers expression of the proapoptotic protein Hid. In addition, our results strongly suggest that, during wing disc morphogenesis, the EGFR pathway protects cells undergoing cell shape changes upon ECM detachment from anoikis. Furthermore, we show that oncogenic activation of the EGFR/Ras pathway in integrin mutant cells rescues them from apoptosis while promoting their extrusion from the epithelium. Altogether, our results support the idea that integrins promote cell survival during normal tissue morphogenesis and prevent the extrusion of transformed cells.This work was funded by project grants from the Ministerio Español de Ciencia, Innovación y Universidades (MICINN, https://www.ciencia.gob.es/) awarded to MDMB (Nos. BFU2016-80797-R and PID2019-109013GB-100) and from the Junta de Andalucía (Proyecto de Excelencia). AV-E was supported by the PID2019-109013GB-100. We are also grateful to the MdM Unit of Excellence GEM (http:// cellcollectives.com/) and to Junta de Andalucía for their continuous funding and support

Integrins positively regulate cell survival in the wing imaginal disc in Drosophila melanogaster

Resumen del póster presentado al 11th Meeting of the Spanish Society for Developmental Biology, celebrado en Girona (España) del 19 al 21 de octubre de 2016.Integrins are a widely expressed family of transmembrane receptors that binds preferentially extracellular matrix components. Integrins can provide mechanical links and activate different pathways, thus regulating various cellular processes, including cell survival. In fact, disruption of integrin function results in a class of apoptosis called anoikis. Although there is a lot of information about the role of integrins in promoting cell survival in cell culture experiments, little is known about its role during morphogenesis. In this study we aim to better understand the role of integrins in regulating cell survival during development using Drosophila wing imaginal disc as a model system. We show that loss of integrin function in the wing disc results in caspase dependent anoikis and cell extrusion. Removal of integrins results in ectopic activation of JNK pathway, which in turn leads to an increase in the expression of the proapoptotic gene hid. These results suggest that integrins regulate cell survival by inhibiting hid expression through downregulation of JNK pathway. In addition, loss of integrin function results in an increase in myosin tension which per se has shown to induce cell death and extrusion. Moreover, blocking cell death in a lack of integrin function context does not prevent cell extrussion. Given these results we would like to propose that elimination of integrin function results in an increase in tension and cellular extrusion that precludes cell death. Thus, in a physiological context integrins would act as mechanosensors and could regulate cell survival in part by controlling cellular tension.Peer reviewe

Integrins act as mechanosensors to regulate cell survival in Drosophila wing imaginal disc

Trabajo presentado en la 59th Annual Drosophila Research Conference, celebrada en Philadelphia (Estados Unidos) del 11 al 15 de abril de 2018