Ginés Morata

Minutes: Mutants of Drosophila autonomously affecting cell division rate☆

Abstract “Minute” (M) mutants of Drosophila show a characteristic prolongation of developmental time. We chose three different Minute mutants to examine the proposition that this slower rate of development is also reflected in a decreased mitotic rate in imaginal disc cells. The division rate of normal cells (M+) dividing in Minute individuals and of Minute cells dividing in normal individuals has been analyzed by inducing mitotic recombination in the growing wing disc and the abdominal histoblasts. In both kinds of experiments, clones of non-Minute cells are always larger than simultaneously arising Minute cell clones implying a higher mitotic rate for M+, as compared to M, cells. In addition, Minute cells seem to be unable to compete with normal cells in the wing disc; however, their viability in the abdominal histoblasts is nearly normal. The possibility of inducing, at any developmental age, cells with different cell-cycle lengths and clones that are larger or smaller than normal provides a powerful new technique with which to approach developmental problems.

Colinearity and functional hierarchy among genes of the homeotic complexes

Homeotic genes identify structures along the anterior to posterior axis during the development of most animals. These genes are clustered into complexes, and their positions within the cluster correlates with their time of expression and the positions of the anterioposterior boundaries of their expression domains. Functional analyses have revealed that this specific genetic order also coincides with a functional hierarchy among members of these complexes, so that the products of more posterior genes in the cluster tend to be prevalent over those of more anterior genes.

Cells compete for Decapentaplegic survival factor to prevent apoptosis in Drosophila wing development

During the growth of Drosophila imaginal discs a process called ‘cell competition’ eliminates slow-proliferating but otherwise viable cells. We report here that cell competition requires the function of the brinker (brk) gene, whose expression is normally repressed by Decapentaplegic (Dpp) signalling but is upregulated in slow-growing Minute/+ cells. Excess brk expression activates the c-Jun amino-terminal kinase pathway, which in turn triggers apoptosis in these cells. We propose that slow-proliferating cells upregulate Brk levels owing to a disadvantage in competing for, or in transducing, the Dpp survival signal. This sequence of events might represent a general mechanism by which weaker cells are eliminated from a growing population, and might serve as a method of controlling cell number and optimizing tissue fitness and hence organ function.

Developmental compartmentalization in the dorsal mesothoracic disc of Drosophila

Abstract The clonal analysis of the development of the dorsal mesothoracic (wing) disc shows that clones initiated after a given time do not cross over certain demarcation lines in the adult cuticle. The property of M + M + (non-Minute) recombinant cells to overgrow the M M + background cells was used to demonstrate the establishment of clonal restrictions during development. It has been shown that M + M + clones initiated at a given time of development share common demarcation lines that delimit what we call “a developmental compartment.” As development time and cell proliferation of the anlage proceed, large compartments become split into pairs of smaller ones. A study of the number of cells in a given compartment at the time of its splitting into subcompartments indicates that the “developmental segregation” takes place in groups of neighboring cells and suggests that the number of segregated cells is different and characteristic for each compartment. Within a given compartment, a single clone of M + M + cells gives rise to 60–90% of the total number of adult cells. This phenomenon is reminiscent of the regulative properties of the morphogenetic fields, and the relation of these to developmental compartments is discussed. Since homoeotic mutants transform entire developmental compartments into one another, the hypothesis is advanced that homoeotic genes control compartment development.

The developmental effect of overexpressing a Ubx product in Drosophila embryos is dependent on its interactions with other homeotic products

We report the developmental effects of expressing an Ultrabithorax (Ubx) product under the hsp70 promoter. Heat induction gives rise to a high, ubiquitous expression of Ubx product that lasts for several hours. We find that whether or not the overexpression of Ubx has a developmental effect on a particular body region of the larva depends on the interactions with the resident homeotic genes. In head and thorax the Ubx product overrides Sex combs reduced, Antennapedia, and probably other homeotic genes and dictates its own developmental program. In abdominal segments A1-A8 the overexpressed Ubx product establishes a normal pattern, alone (A1) or in combination with abdominal-A (A2-A4) and Abdominal-B (A5-A8), indicating that the excess of product is irrelevant. In segment A9 the highly expressed Ubx product is phenotypically suppressed by the r product of Abdominal-B. The presence of high levels of Ubx protein is also irrelevant in the telson.

The role of buttonhead and Sp1 in the development of the ventral imaginal discs of Drosophila.

The related genes buttonhead (btd) and Drosophila Sp1 (the Drosophila homologue of the human SP1 gene) encode zinc-finger transcription factors known to play a developmental role in the formation of the Drosophila head segments and the mechanosensory larval organs. We report a novel function of btd and Sp1: they induce the formation and are required for the growth of the ventral imaginal discs. They act as activators of the headcase (hdc) and Distal-less (Dll) genes, which allocate the cells of the disc primordia. The requirement for btd and Sp1 persists during the development of ventral discs: inactivation by RNA interference results in a strong reduction of the size of legs and antennae. Ectopic expression of btd in the dorsal imaginal discs (eyes, wings and halteres) results in the formation of the corresponding ventral structures (antennae and legs). However, these structures are not patterned by the morphogenetic signals present in the dorsal discs; the cells expressing btd generate their own signalling system, including the establishment of a sharp boundary of engrailed expression, and the local activation of the wingless and decapentaplegic genes. Thus, the Btd product has the capacity to induce the activity of the entire genetic network necessary for ventral imaginal discs development. We propose that this property is a reflection of the initial function of the btd/Sp1 genes that consists of establishing the fate of the ventral disc primordia and determining their pattern and growth.

The Wingless target gene Dfz3 encodes a new member of the Drosophila Frizzled family

Here we report the identification of Dfz3, a novel member of the Frizzled family of seven-pass transmembrane receptors. Like Dfz2, Dfz3 is a target gene of Wingless (Wg) signalling, but in contrast to Dfz2, it is activated rather than repressed by Wg signalling in imaginal discs. We show that Dfz3 is not required for viability but is necessary for optimal Wg signalling at the wing margin.

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. This feature makes them a convenient system to study reprogramming during regeneration. We find that massive damage inflicted to the posterior or the dorsal compartment of the wing disc causes a transient breakdown of compartment boundaries, which are quickly reconstructed. The cells involved in the reconstruction often modify their original identity, visualized by changes in the expression of developmental genes like engrailed or cubitus interruptus. This reprogramming is mediated by up regulation of the JNK pathway and transient debilitation of the epigenetic control mechanism. Our results also show that the local developmental context plays a role in the acquisition of new cell identities: cells expressing engrailed induce engrailed expression in neighbor cells. DOI: http://dx.doi.org/10.7554/eLife.01831.001

Behaviour in aggregates of irradiated imaginal disk cells ofDrosophila

SummaryThe ability of dissociated cells to reaggregate, grow in culture (in vivo) and differentiate cuticular structures following increasing doses of X-ray radiation has been studied.At low doses (up to 5 Kr) reaggregation, but not cell viability, is affected. The reaggregation ability of irradiated cells is improved with increasing time between irradiation and aggregation and can be rescued by mixing irradiated and non-irradiated cells.On the contrary, growth and cell differentiation seem to be cell autonomous events. At doses between 5 Kr and 8 Kr cell proliferation is impaired, and after doses over 10 Kr reaggregates show a “negative growth.” The differentiation of cuticular structures, such as chaetes and trichomes, show a different X-ray sensitivity.A unifying interpretation of these results is outlined in the discussion.

Cells in search of a signal

During development, cells communicate by sending and receiving signals over long distances. New findings indicate that target cells may pick up signals by projecting long cytoplasmic extensions to the point at which the signals are produced.