Size compensation in after generalised cell death.

Regeneration is a response mechanism aimed to restore tissues that have been damaged. We are studying in the wing disc of the regenerative response to a dose of Ionizing Radiation that kills over 35% of the cells distributed all over the disc. After such treatment the discs are able to restore normal size, indicating there is a mechanism that repairs generalised damage.

Lack of apoptosis leads to cellular senescence and tumorigenesis in Drosophila epithelial cells.

Programmed cell death (apoptosis) is a homeostasis program of animal tissues designed to remove cells that are unwanted or are damaged by physiological insults. To assess the functional role of apoptosis, we have studied the consequences of subjecting Drosophila epithelial cells defective in apoptosis to stress or genetic perturbations that normally cause massive cell death. We find that many of those cells acquire persistent activity of the JNK pathway, which drives them into senescent status, characterized by arrest of cell division, cell hypertrophy, Senescent Associated ß-gal activity (SA-ß-gal), reactive oxygen species (ROS) production, Senescent Associated Secretory Phenotype (SASP) and migratory behaviour.

An exciting period of Drosophila developmental biology: Of imaginal discs, clones, compartments, parasegments and homeotic genes.

In this review we recall a number of important discoveries that took place in Drosophila during the seventies and eighties of the last century. The development of cell lineage methods and of powerful modifications of same, such as the Minute technique, led to the discovery of compartments and provided a clearer picture of the body organization: that came to be seen as a chain of metameric lineage units along the A/P body axis. Further, genetic screens allowed the identification of the genes involved in the establishment of the metameric scaffold - the segmentation genes- and also of Hox genes that are responsible for the specific development of individual body parts.

Chromatin remodelling and retrotransposons activities during regeneration in Drosophila.

Regeneration is a response mechanism aiming to reconstruct lost or damaged structures. To achieve this, the cells repopulating the lost tissue often have to change their original identity, a process that involves chromatin remodelling.We have analysed the issue of chromatin remodelling during regeneration in the wing disc of Drosophila .

Tumorigenesis and cell competition in in the absence of function.

Cell competition is a homeostatic process that eliminates by apoptosis unfit or undesirable cells from animal tissues, including tumor cells that appear during the life of the organism. In there is evidence that many types of oncogenic cells are eliminated by cell competition. One exception is cells mutant for (), a member of the Polycomb family of genes; most of the isolated mutant clones survive and develop tumorous overgrowths in imaginal discs.

Cell competition: A historical perspective.

Cell competition is a homeostatic process designed to remove from animal tissues viable cells that are unfit, abnormal or malignant and that may compromise the general fitness or the viability of the organism. Originally discovered in Drosophila in the mid-seventies of last century, there is strong evidence that it also occurs in other metazoans, where cell competition appears to play a similar surveillance role. In this review I summarize the field of cell competition, with special emphasis in the history of the phenomenon within the general frame of Developmental Biology in the second half of the XX century, pointing out the key observations and the evolution of ideas that have led to the current understanding.

JNK-mediated Slit-Robo signaling facilitates epithelial wound repair by extruding dying cells.

Multicellular organisms repair injured epithelium by evolutionarily conserved biological processes including activation of c-Jun N-terminal kinase (JNK) signaling. Here, we show in Drosophila imaginal epithelium that physical injury leads to the emergence of dying cells, which are extruded from the wounded tissue by JNK-induced Slit-Roundabout2 (Robo2) repulsive signaling. Reducing Slit-Robo2 signaling in the wounded tissue suppresses extrusion of dying cells and generates aberrant cells with highly upregulated growth factors Wingless (Wg) and Decapentaplegic (Dpp).

Cell competition and tumorigenesis in the imaginal discs of Drosophila.

Cancer is a major health issue and the object of investigations in thousands of laboratories all over the world. Most of cancer research is being carried out in in vitro systems or in animal models, generally mice or rats. However, the discovery of the high degree of genetic identity among metazoans has prompted investigation in organisms like Drosophila, on the idea that the genetic basis of cancer in flies and humans may have many aspects in common.

A refutation to 'A new A-P compartment boundary and organizer in holometabolous insect wings'.

We respond to a recent report by Abbasi and Marcus who present two main findings: first they argue that there is an organiser and a compartment boundary within the posterior compartment of the butterfly wing. Second, they present evidence for a previously undiscovered lineage boundary near wing vein 5 in Drosophila, a boundary that delineates a "far posterior" compartment. Clones of cells were marked with the yellow mutation and they reported that these clones always fail to cross a line close to vein 5 on the Drosophila wing.

Pro-apoptotic and pro-proliferation functions of the JNK pathway of Drosophila: roles in cell competition, tumorigenesis and regeneration.

The Jun N-terminal kinase (JNK) is a member of the mitogen-activated protein kinase family. It appears to be conserved in all animal species where it regulates important physiological functions involved in apoptosis, cell migration, cell proliferation and regeneration. In this review, we focus on the functions of JNK in Drosophila imaginal discs, where it has been reported that it can induce both cell death and cell proliferation.

Regenerative response of different regions of Drosophila imaginal discs.

Thanks to the introduction of new methods to induce massive damage under controlled conditions, much information about regeneration in Drosophila imaginal discs has accumulated in recent years. In this review, we discuss results concerning primarily the wing disc, putting emphasis on the different regenerative responses of the wing appendage, which exhibits a robust regenerative potential, and the trunk region, the notum, which regenerates very poorly. The wing disc may be a paradigm of a tissue in which a common original lineage generates cells with distinct regenerative potential.

Short-term activation of the Jun N-terminal kinase pathway in apoptosis-deficient cells of Drosophila induces tumorigenesis.

In Drosophila, the JNK pathway eliminates by apoptosis aberrant cells that appear in development. It also performs other functions associated with cell proliferation, but analysis of the latter is hindered by the pro-apoptotic activity. We report the response of apoptosis-deficient cells to transient activation of JNK and show that it causes persistent JNK function during the rest of the development.

Distinct regenerative potential of trunk and appendages of mediated by JNK signalling.

The body comprises a central part, the trunk, and outgrowths of the trunk, the appendages. Much is known about appendage regeneration, but little about the trunk. As the wing imaginal disc contains a trunk component, the notum, and a wing appendage, we have investigated the response to ablation of these two components.

Homeostatic response to blocking cell division in Drosophila imaginal discs: Role of the Fat/Dachsous (Ft/Ds) pathway.

One major problem in developmental biology is the identification of the mechanisms that control the final size of tissues and organs. We are addressing this issue in the imaginal discs of Drosophila by analysing the response to blocking cell division in large domains in the wing and leg discs. The affected domains may be zones of restricted lineage like compartments, or zones of open lineage that may integrate cells from the surrounding territory.

Cell reprogramming during regeneration in Drosophila: transgression of compartment boundaries.

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.

Tumorigenic Properties of Drosophila Epithelial Cells Mutant for lethal giant larvae.

Background: Mutations in Drosophila tumor suppressor genes (TSGs) lead to the formation of invasive tumors in the brain and imaginal discs.

Results: Here we studied the tumorigenic properties of imaginal discs mutant for the TSG gene lethal giant larvae (lgl). lgl mutant cells display the characteristic features of mammalian tumor cells: they can proliferate indefinitely, induce additional tracheogenesis (an insect counterpart of vasculogenesis) and invade neighboring tissues.

Cell competition, apoptosis and tumour development.

The phenomenon of cell competition is an interactive process originally discovered in the imaginal discs of Drosophila; it is a developmental mechanism that identifies and eliminates cells that are weaker than their neighbours or have features that make them different or not well adapted to their surroundings. It appears to be an important homeostatic mechanism to contribute to the general fitness of developing tissues. Here we discuss some of the basic features of cell competition and then focus on results indicating that cell competition is responsible for the removal of malignant or aberrant cells that may appear during development, although in certain circumstances it can revert its role to promote tumour growth.

Transgressions of compartment boundaries and cell reprogramming during regeneration in Drosophila.

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.

Eiger triggers death from afar.

Cells undergoing programmed cell death release signals that can trigger the death of cells at remote locations.

Tissue homeostasis in the wing disc of Drosophila melanogaster: immediate response to massive damage during development.

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.

Mitogenic signaling from apoptotic cells in Drosophila.

Apoptotic cells of Drosophila not only activate caspases, but also are able to secrete developmental signals like Hedgehog (Hh), Decapentaplegic (Dpp) and Wingless (Wg) before dying. Since Dpp and Wg are secreted in growing tissues and behave as growth factors, it was proposed that they play a role in compensatory proliferation, the process by which a growing blastema can restore normal size after massive apoptosis. We discuss recent results showing that there is normal compensatory proliferation in the absence of Dpp/Wg signaling, thus indicating it has no significant role in the process.

A tumor-suppressing mechanism in Drosophila involving cell competition and the Hippo pathway.

Mutant larvae for the Drosophila gene lethal giant larva (lgl) develop neoplastic tumors in imaginal discs. However, lgl mutant clones do not form tumors when surrounded by wild-type tissue, suggesting the existence of a tumor-suppressing mechanism. We have investigated the tumorigenic potential of lgl mutant cells by generating wing compartments that are entirely mutant for lgl and also inducing clones of various genetic combinations of lgl(-) cells.

Differential division rates and size control in the wing disc.

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.