Search PubMed⌕ Search

Biomedical subjects

Heinrich Jasper

Publications and source records attributed to Heinrich Jasper.

10 recordsLinked to original sources
PubMed2006

Foxo and Fos regulate the decision between cell death and survival in response to UV irradiation.

Cells damaged by environmental insults have to be repaired or eliminated to ensure tissue homeostasis in metazoans. Recent studies suggest that the balance between cell survival signals and pro-apoptotic stimuli controls the decision between cell repair and death. How these competing signals are integrated and interpreted to achieve accurate control over cell fate in vivo is incompletely understood. Here, we show that the Forkhead Box O transcription factor Foxo and the AP-1 transcription factor DFos are required downstream of Jun-N-terminal kinase signaling for the apoptotic response to UV-induced DNA damage in the developing Drosophila retina. Both transcription factors regulate the pro-apoptotic gene hid. Our results indicate that UV-induced apoptosis is repressed by receptor tyrosine kinase-mediated inactivation of Foxo. These data suggest that integrating stress and survival signals through Foxo drives the decision between cell death and repair of damaged cells in vivo.

Animals↗
PubMed2006

JNK signaling coordinates integrin and actin functions during Drosophila embryogenesis.

Epithelial movements are key morphogenetic events in animal development. They are driven by multiple mechanisms, including signal-dependent changes in cytoskeletal organization and in cell adhesion. Such processes must be controlled precisely and coordinated to accurately sculpt the three-dimensional form of the developing organism. By observing the Drosophila epidermis during embryonic development using confocal time-lapse microscopy, we have investigated how signaling through the Jun-N-terminal kinase (JNK) pathway governs the tissue sheet movements that result in dorsal closure (DC). We find that JNK controls the polymerization of actin into a cable at the epidermal leading edge as previously suggested, as well as the joining (zipping) of the contralateral epithelial cell sheets. Here, we show that zipping is mediated by regulation of the integrins myospheroid and scab. Our data demonstrate that JNK signaling regulates a set of target genes that cooperate to facilitate epithelial movement and closure.

Actins↗
PubMed2006

Migration in action: profiling border cells.

Acquiring the ability to migrate is essential for cells taking part in many developmental and disease processes. Two studies in this issue of Developmental Cell use gene expression profiling of purified border cells from the Drosophila ovary to characterize the molecular changes required in cells to initiate migration in vivo. Their results offer interesting new insights into a moving cell's physiology.

Animals↗
PubMed2005

Non-cell-autonomous induction of tissue overgrowth by JNK/Ras cooperation in a Drosophila tumor model.

The role of c-Jun N-terminal kinase (JNK) signaling in cancer is enigmatic, and both tumor-promoting and tumor-suppressing functions have been ascribed to JNK pathway components. We have used the Drosophila eye to investigate the function of the JNK pathway in three different tumor models of increasing malignancy. Benign lesions caused by loss of the neoplastic tumor suppressor gene scribble can efficiently be eliminated by JNK-induced apoptosis. In such a scenario, the eye reverts to a wild-type phenotype, indicating that the JNK pathway prevents tumor formation. The situation changes in the case of aggressive tissue overgrowth, which can be induced by oncogenic activation of the Ras/Raf pathway in the eye, or in malignant invasive tumors resulting when Raf activation is combined with loss of scribble. The growth of these more aggressive tumor types is significantly, yet incompletely, suppressed by JNK-mediated apoptosis. Remarkably, oncogenic Raf and JNK cooperate in these tumors, to induce massive hyperplasia in adjacent wild-type tissue. Thus, depending on the genetic context, JNK signaling can eradicate tumors by removing premalignant cells, or promote aberrant overgrowth in tissues surrounding primary lesions.

Animals↗
PubMed2005

Synaptic and genomic responses to JNK and AP-1 signaling in Drosophila neurons.

BACKGROUND: The transcription factor AP-1 positively controls synaptic plasticity at the Drosophila neuromuscular junction. Although in motor neurons, JNK has been shown to activate AP-1, a positive regulator of growth and strength at the larval NMJ, the consequences of JNK activation are poorly studied. In addition, the downstream transcriptional targets of JNK and AP-1 signaling in the Drosophila nervous system have yet to be identified. Here, we further investigated the role of JNK signaling at this model synapse employing an activated form of JNK-kinase; and using Serial Analysis of Gene Expression and oligonucleotide microarrays, searched for candidate early targets of JNK or AP-1 dependent transcription in neurons. RESULTS: Temporally-controlled JNK induction in postembryonic motor neurons triggers synaptic growth at the NMJ indicating a role in developmental plasticity rather than synaptogenesis. An unexpected observation that JNK activation also causes a reduction in transmitter release is inconsistent with JNK functioning solely through AP-1 and suggests an additional, yet-unidentified pathway for JNK signaling in motor neurons. SAGE profiling of mRNA expression helps define the neural transcriptome in Drosophila. Though many putative AP-1 and JNK target genes arose from the genomic screens, few were confirmed in subsequent validation experiments. One potentially important neuronal AP-1 target discovered, CG6044, was previously implicated in olfactory associative memory. In addition, 5 mRNAs regulated by RU486, a steroid used to trigger conditional gene expression were identified. CONCLUSION: This study demonstrates a novel role for JNK signaling at the larval neuromuscular junction and provides a quantitative profile of gene transcription in Drosophila neurons. While identifying potential JNK/AP-1 targets it reveals the limitations of genome-wide analyses using complex tissues like the whole brain.

Animals↗
PubMed2005

JNK extends life span and limits growth by antagonizing cellular and organism-wide responses to insulin signaling.

Aging of a eukaryotic organism is affected by its nutrition state and by its ability to prevent or repair oxidative damage. Consequently, signal transduction systems that control metabolism and oxidative stress responses influence life span. When nutrients are abundant, the insulin/IGF signaling (IIS) pathway promotes growth and energy storage but shortens life span. The transcription factor Foxo, which is inhibited by IIS, extends life span in conditions of low IIS activity. Life span can also be increased by activating the stress-responsive Jun-N-terminal kinase (JNK) pathway. Here we show that JNK requires Foxo to extend life span in Drosophila. JNK antagonizes IIS, causing nuclear localization of Foxo and inducing its targets, including growth control and stress defense genes. JNK and Foxo also restrict IIS activity systemically by repressing IIS ligand expression in neuroendocrine cells. The convergence of JNK signaling and IIS on Foxo provides a model to explain the effects of stress and nutrition on longevity.

Active Transport, Cell Nucleus↗
PubMed2005

DREF is required for efficient growth and cell cycle progression in Drosophila imaginal discs.

Based on overexpression studies and target gene analyses, the transcription factor DNA replication-related element factor (DREF) has been proposed to regulate growth and replication in Drosophila melanogaster. Here we present loss-of-function experiments to analyze the contribution of DREF to these processes. RNA interference-mediated extinction of DREF function in vivo demonstrates a requirement for the protein for normal progression through the cell cycle and consequently for growth of imaginal discs and the derived adult organs. We show that DREF regulates the expression of genes that are required for the transition of imaginal disc cells through S phase. In conditions of suppressed apoptosis, DREF activation can cause overgrowth of developing organs. These data establish DREF as a global regulator of transcriptional programs that mediate cell proliferation and organ growth during animal development.

Animals↗
PubMed2003

JNK signaling confers tolerance to oxidative stress and extends lifespan in Drosophila.

Changes in the genetic makeup of an organism can extend lifespan significantly if they promote tolerance to environmental insults and thus prevent the general deterioration of cellular function that is associated with aging. Here, we introduce the Jun N-terminal kinase (JNK) signaling pathway as a genetic determinant of aging in Drosophila melanogaster. Based on expression profiling experiments, we demonstrate that JNK functions at the center of a signal transduction network that coordinates the induction of protective genes in response to oxidative challenge. JNK signaling activity thus alleviates the toxic effects of reactive oxygen species (ROS). In addition, we show that flies with mutations that augment JNK signaling accumulate less oxidative damage and live dramatically longer than wild-type flies. Our work thus identifies the evolutionarily conserved JNK signaling pathway as a major genetic factor in the control of longevity.

Aging↗
PubMed2002

A genomic switch at the transition from cell proliferation to terminal differentiation in the Drosophila eye.

Organogenesis involves cell proliferation followed by complex determination and differentiation events that are intricately controlled in time and space. The instructions for these different steps are, to a large degree, implicit in the gene expression profiles of the cells that partake in organogenesis. Combining fluorescence-activated cell sorting and SAGE, we analyzed genomic expression patterns in the developing eye of Drosophila melanogaster. Genomic activity changes as cells pass from an uncommitted proliferating progenitor state through determination and differentiation steps toward a specialized cell fate. Analysis of the upstream sequences of genes specifically expressed during the proliferation phase of eye development implicates the transcription factor DREF and its inhibitor dMLF in the control of cell growth in this organ.

Animals↗