Asymmetric patterns of gap junctional communication in developing chicken skin

To study the pattern of gap junctional communication in chicken skin and feather development, we injected Lucifer Yellow into single cells and monitored the transfer of the fluorescent dye through gap junctions. Dye coupling is present between cells of the epithelium as well as between cells of the mesoderm. However, dye transfer did not occur equally in all directions and showed several consistent patterns and asymmetries, including: (1) no dye coupling between mesoderm and epithelium, (2) partial restriction of dye coupling at the feather bud/interbud boundary during early feather bud development, (3) preferential distribution of Lucifer Yellow along the anteroposterior axis of the feather placode and (4) absence of dye coupling in some epithelial cells. These results suggest the presence of preferential pathways of communication that may play a role in the patterning of chicken skin

The case of JAK-STAT and EGFR cooperation in oncogenesis

This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License.Drosophila is proving to be a valuable model for studying aggressive tumors induced by the combined activation of EGFR and JAK-STAT signaling. Here we summarize some of the most recent data showing that tissue damage and the modulation of common pathway regulators are at the heart tumor progression and metastasis.Peer reviewe

Halving the selenophosphate synthetase gene dose confers hypersensitivity to oxidative stress in Drosophila melanogaster

AbstractSeveral lines of evidence indicate that selenoproteins mainly act as cellular antioxidants. Here, we test this idea comparing the sensitivity to oxidative stress (paraquat and hydrogen peroxide) between wild type and heterozygous flies for the selenophosphate synthetase selDptuf mutation. Whereas under normal laboratory conditions no difference in life span is observed, a significant decrease is seen in heterozygous flies treated with oxidant agents. In contrast, overexpression of the selD gene in motoneurons did not extend longevity. Our results strongly suggest that selD haploinsufficiency makes heterozygous flies more sensitive to oxidative stress and add further evidence to the role of selenoproteins as cellular antioxidants

Drosophila melanogaster com a organisme model: una font d'informació en recerca biomèdica

Drosophila melanogaster és un exemple d'organisme model des de fa més de cent anys. S'ha utilitzat des d'aleshores com a sistema per investigar alguns dels principis fonamentals de la genètica, la biologia molecular, l'enginyeria genètica, la biologia del desenvolupament i l'evolució. Però en les darreres dècades, Drosophila ha esdevingut un element clau com a font d'informació per entendre les bases genètiques en la recerca biomèdica. En aquest article discutirem alguns exemples de l'ús d'aquest organisme model.Drosophila melanogaster as a model system: a source of information for biomedical research. Drosophila melanogaster is an example of model organism since a hundred years ago. It has been used as a model system to investigate the basic principles of genetics, molecular biology, genetic engineering, developmental biology and evolution. But in the last decades, Drosophila has become key for the understanding of the genetic basis of diseases in biomedical research. In this article we will discuss some of the relevant features of Drosophila as model organism

Ash2 acts as an ecdysone receptor coactivator by stabilizing the histone methyltransferase Trr.

The molting hormone ecdysone triggers chromatin changes via histone modifications that are important for gene regulation. On hormone activation, the ecdysone receptor (EcR) binds to the SET domain-containing histone H3 methyltransferase trithorax-related protein (Trr). Methylation of histone H3 at lysine 4 (H3K4me), which is associated with transcriptional activation, requires several cofactors, including Ash2. We find that ash2 mutants have severe defects in pupariation and metamorphosis due to a lack of activation of ecdysone-responsive genes. This transcriptional defect is caused by the absence of the H3K4me3 marks set by Trr in these genes. We present evidence that Ash2 interacts with Trr and is required for its stabilization. Thus we propose that Ash2 functions together with Trr as an ecdysone receptor coactivator

Functional dissection of the ash2 and ash1 transcriptomes provides insights into the transcriptional basis of wing phenotypes and reveals conserved protein interactions

Analysis of the gene expression profiles of wing imaginal discs from ash2 and ash1 mutants shows that they are highly similar, supporting a model in which they act together to maintain stable states of transcription

Role of D-GADD45 in JNK-Dependent Apoptosis and Regeneration in Drosophila

The GADD45 proteins are induced in response to stress and have been implicated in the regulation of several cellular functions, including DNA repair, cell cycle control, senescence, and apoptosis. In this study, we investigate the role of D-GADD45 during Drosophila development and regeneration of the wing imaginal discs. We find that higher expression of D-GADD45 results in JNK-dependent apoptosis, while its temporary expression does not have harmful effects. Moreover, D-GADD45 is required for proper regeneration of wing imaginal discs. Our findings demonstrate that a tight regulation of D-GADD45 levels is required for its correct function both, in development and during the stress response after cell death

Conserved chromosomal clustering of genes governed by chromatin regulators in Drosophila

Transcriptional analysis of chromatin regulator mutants in Drosophila melanogaster identified clusters of functionally related genes conserved in other insect species

Oxidative Stress Is Associated with Overgrowth in Drosophila l(3)mbt Mutant Imaginal Discs

The loss-of-function conditions for an l(3)malignant brain tumour (l(3)mbt) in larvae reared at 29 degrees C results in malignant brain tumours and hyperplastic imaginal discs. Unlike the former that have been extensively characterised, little is known about the latter. Here we report the results of a study of the hyperplastic l(3)mbt mutant wing imaginal discs. We identify the l(3)mbt wing disc tumour transcriptome and find it to include genes involved in reactive oxygen species (ROS) metabolism. Furthermore, we show the presence of oxidative stress in l(3)mbt hyperplastic discs, even in apoptosis-blocked conditions, but not in l(3)mbt brain tumours. We also find that chemically blocking oxidative stress in l(3)mbt wing discs reduces the incidence of wing disc overgrowths. Our results reveal the involvement of oxidative stress in l(3)mbt wing discs hyperplastic growth

Ask1 and Akt act synergistically to promote ROS-dependent regeneration in Drosophila

How cells communicate to initiate a regenerative response after damage has captivated scientists during the last few decades. It is known that one of the main signals emanating from injured cells is the Reactive Oxygen Species (ROS), which propagate to the surrounding tissue to trigger the replacement of the missing cells. However, the link between ROS production and the activation of regenerative signaling pathways is not yet fully understood. We describe here the non-autonomous ROS sensing mechanism by which living cells launch their regenerative program. To this aim, we used Drosophila imaginal discs as a model system due to its well-characterized regenerative ability after injury or cell death. We genetically-induced cell death and found that the Apoptosis signal-regulating kinase 1 (Ask1) is essential for regenerative growth. Ask1 senses ROS both in dying and living cells, but its activation is selectively attenuated in living cells by Akt1, the core kinase component of the insulin/insulin-like growth factor pathway. Akt1 phosphorylates Ask1 in a secondary site outside the kinase domain, which attenuates its activity. This modulation of Ask1 activity results in moderate levels of JNK signaling in the living tissue, as well as in activation of p38 signaling, both pathways required to turn on the regenerative response. Our findings demonstrate a non-autonomous activation of a ROS sensing mechanism by Ask1 and Akt1 to replace the missing tissue after damage. Collectively, these results provide the basis for understanding the molecular mechanism of communication between dying and living cells that triggers regeneration