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H Steller

Publications and source records attributed to H Steller.

At least 37 records · Page 2Linked to original sources
PubMed1997

Cooperative functions of the reaper and head involution defective genes in the programmed cell death of Drosophila central nervous system midline cells.

In Drosophila, the chromosomal region 75C1-2 contains at least three genes, reaper (rpr), head involution defective (hid), and grim, that have important functions in the activation of programmed cell death. To better understand how cells are killed by these genes, we have utilized a well defined set of embryonic central nervous system midline cells that normally exhibit a specific pattern of glial cell death. In this study we show that both rpr and hid are expressed in dying midline cells and that the normal pattern of midline cell death requires the function of multiple genes in the 75C1-2 interval. We also utilized the P[UAS]/P[Gal4] system to target expression of rpr and hid to midline cells. Targeted expression of rpr or hid alone was not sufficient to induce ectopic midline cell death. However, expression of both rpr and hid together rapidly induced ectopic midline cell death that resulted in axon scaffold defects characteristic of mutants with abnormal midline cell development. Midline-targeted expression of the baculovirus p35 protein, a caspase inhibitor, blocked both normal and ectopic rpr- and hid-induced cell death. Taken together, our results suggest that rpr and hid are expressed together and cooperate to induce programmed cell death during development of the central nervous system midline.

Animals↗
PubMed1997

DCP-1, a Drosophila cell death protease essential for development.

Apoptosis, a form of cellular suicide, involves the activation of CED-3-related cysteine proteases (caspases). The regulation of caspases by apoptotic signals and the precise mechanism by which they kill the cell remain unknown. In Drosophila, different death-inducing stimuli induce the expression of the apoptotic activator reaper. Cell killing by reaper and two genetically linked apoptotic activators, hid and grim, requires caspase activity. A Drosophila caspase, named Drosophila caspase-1 (DCP-1), was identified and found to be structurally and biochemically similar to Caenorhabditis elegans CED-3. Loss of zygotic DCP-1 function in Drosophila caused larval lethality and melanotic tumors, showing that this gene is essential for normal development.

Amino Acid Sequence↗
PubMed1997

Facing death in the fly: genetic analysis of apoptosis in Drosophila.

Apoptosis, a gene-directed form of cell death, occurs normally during development and plays a major role in many diseases, including cancer and neurodegenerative disorders. Molecular genetic studies in Drosophila have revealed the existence of three novel apoptotic activators, reaper, head involution defective and grim. Additionally, Drosophila homologs of evolutionarily conserved IAPs (inhibitor of apoptosis proteins) and CED-3/ICE-like proteases have been identified and characterized. Through the combined use of genetic, molecular, biochemical and cell biological techniques in Drosophila it should now be possible to elucidate the precise mechanism by which apoptosis occurs, and how the death program is activated in response to many distinct death-inducing signals.

Animals↗
PubMed1997

Disruption of a behavioral sequence by targeted death of peptidergic neurons in Drosophila.

The neuropeptide eclosion hormone (EH) is a key regulator of insect ecdysis. We tested the role of the two EH-producing neurons in Drosophila by using an EH cell-specific enhancer to activate cell death genes reaper and head involution defective to ablate the EH cells. In the EH cell knockout flies, larval and adult ecdyses were disrupted, yet a third of the knockouts emerged as adults, demonstrating that EH has a significant but nonessential role in ecdysis. The EH cell knockouts had discrete behavioral deficits, including slow, uncoordinated eclosion and an insensitivity to ecdysis-triggering hormone. The knockouts lacked the lights-on eclosion response despite having a normal circadian eclosion rhythm. This study represents a novel approach to the dissection of neuropeptide regulation of a complex behavioral program.

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PubMed1996

Activation of the reaper gene during ectopic cell killing in Drosophila.

The product of the reaper (rpr) gene is required for programmed cell death in Drosophila. We examined rpr expression during ectopic cell deaths caused by ionizing radiation or aberrant development. In both instances, dramatic induction of rpr expression was observed. A genomic fragment upstream of rpr confers this regulatory behavior upon a lacZ reporter transgene. In a model cell culture system, conditional expression of REAPER is sufficient to induce massive apoptosis that can be prevented by the anti-apoptotic protein p35. Overall, these results suggest that diverse signals converge at, or upstream of, rpr-associated transcriptional regulatory elements that can function to initiate a common apoptotic pathway involving ICE-like protease activity.

Animals↗
PubMed1996

Cell killing by the Drosophila gene reaper.

The reaper gene (rpr) is important for the activation of apoptosis in Drosophila. To investigate whether rpr expression is sufficient to induce apoptosis, transgenic flies were generated that express rpr complementary DNA or the rpr open reading frame in cells that normally live. Transcription of rpr from a heat-inducible promoter rapidly caused wide-spread ectopic apoptosis and organismal death. Ectopic overexpression of rpr in the developing retina resulted in eye ablation. The occurrence of cell death was highly sensitive to the dosage of the transgene. Because cell death induced by the protein encoded by rpr (RPR) could be blocked by the baculovirus p35 protein, RPR appears to activate a death program mediated by a ced-3/ICE (interleukin-1 converting enzyme)-like protease.

Animals↗
PubMed1996

Positional information along the dorsal-ventral axis of the Drosophila eye: graded expression of the four-jointed gene.

Several observations suggest that developing ommatidia in the Drosophila eye have distinct dorsal-ventral (d-v) positional identities, despite their morphological uniformity. To identify molecular differences along the d-v axis of the eye, we carried out a systematic screen for P-element insertions that show nonuniform reporter gene expression along this axis. We identified P-element insertions in which lacZ expression is activated in dorsal, ventral, or equatorial regions of the disc. These patterns of transcriptional enhancer activity are established early in disc development and are maintained in a size invariant manner during disc growth. Several insertions with an equatorial-to-polar gradient of lacZ expression disrupt the four-jointed (fj) gene which is required for proper leg, wing, and eye development. The fj cDNA sequence includes a presumptive internal signal sequence, indicating that fj encodes a cell surface or secreted protein. Analysis of the fj phenotype and expression pattern in the leg suggests that fj is required for cell-cell signaling during disc development.

Amino Acid Sequence↗
PubMed1996

Migration of glial cells into retinal axon target field in Drosophila melanogaster.

During the development of the Drosophila visual system, photoreceptor (retinal) axons (R axons) project retino-topically to their targets in the optic lobes. The establishment of this precise pattern of connections does not depend on interactions between adjacent axon bundles, suggesting that R axons rely on environmental signals for proper pathfinding. Glial cells that are located along the R-axon trajectory are likely candidates to provide guidance cues for R-axon navigation. This study defines the origin of lamina glia (L glia), and demonstrates that L glia migrate into the lamina over a considerable distance. Glia are located in positions at which the R axons make critical growth choices. In the absence of cues from the eye, several classes of glia migrate to their final positions within the optic lobe anlage and begin to differentiate. Our results are consistent with a role for the glia in providing guidance cues to the R axons.

Animals↗
PubMed1996

Molecular and genetic analyses of lama, an evolutionarily conserved gene expressed in the precursors of the Drosophila first optic ganglion.

Drosophila retinal axons trigger both the proliferation of their targets, the lamina neurons, as well as the final differentiation and migration of the lamina glia. To date, the molecular basis of these interactions has remained unclear. We have identified a new gene, lamina ancestor (lama). Both the lamina's neural and glial progenitors express lama, even though these cells have very different developmental origins. Expression of lama is down-regulated once the precursors begin their differentiation programs. Loss of function mutants are viable and fertile, and appear to have normally developed visual systems. lama encodes a novel protein that is 74% identical to its D. virilis homologue.

Amino Acid Sequence↗
PubMed1995

The head involution defective gene of Drosophila melanogaster functions in programmed cell death.

Deletions of chromosomal region, 75C1,2 block virtually all programmed cell death (PCD) in the Drosophila embryo. We have identified a gene previously in this interval, reaper (rpr), which encodes an important regulator of PCD. Here we report the isolation of a second gene in this region, head involution defective (hid), which plays a similar role in PCD. hid mutant embryos have decreased levels of cell death and contain extra cells in the head. We have cloned the hid gene and find that its expression is sufficient to induce PCD in cell death defective mutants. The hid gene appears to encode a novel 410-amino-acid protein, and its mRNA is expressed in regions of the embryo where cell death occurs. Ectopic expression of hid in the Drosophila retina results in eye ablation. This phenotype can be suppressed completely by expression of the anti-apoptotic p35 protein from baculovirus, indicating that p35 may act genetically downstream from hid.

Alleles↗
PubMed1995

Mechanisms and genes of cellular suicide.

Apoptosis is a morphologically distinct form of programmed cell death that plays a major role during development, homeostasis, and in many diseases including cancer, acquired immunodeficiency syndrome, and neurodegenerative disorders. Apoptosis occurs through the activation of a cell-intrinsic suicide program. The basic machinery to carry out apoptosis appears to be present in essentially all mammalian cells at all times, but the activation of the suicide program is regulated by many different signals that originate from both the intracellular and the extracellular milieu. Genetic studies in the nematode Caenorhabditis elegans and in the fruit fly Drosophila melanogaster have led to the isolation of genes that are specifically required for the induction of programmed cell death. At least some components of the apoptotic program have been conserved among worms, insects, and vertebrates.

Animals↗
PubMed1995

Establishment of neuronal connectivity during development of the Drosophila larval visual system.

We used confocal microscopy in conjunction with specific antibodies and enhancer trap strains to investigate the development of specific neuronal connections in a simple model system, the larval visual system of Drosophila. We find that the establishment of axonal projections from the larval photoreceptor neurons to their central nervous system targets involves a series of discrete steps. During embryogenesis, the larval optic nerve contacts several different cell types, including optic lobe pioneer (OLP) neurons and a number of glial cells. We demonstrate that OLP neurons are present and project normally in glass (gl) mutant embryos in which the larval optic nerve fails to develop, suggesting that they do not depend on interactions with the larval optic nerve for differentiation and proper axonal projection. The OLPs fail to differentiate properly is disconnected (disco) mutant embryos, where appropriate connections between the larval optic nerve and its targets in the brain are not formed. The disco gene is expressed in the OLPs and may therefore act autonomously to direct the differentiation of these cells. Taken together, our results suggest that the OLPs act as an intermediate target required for the establishment of normal optic nerve projection and connectivity.

Animals↗
PubMed1995

The control of apoptosis in Drosophila.

Although several genes involved in apoptosis have been identified recently, the mechanisms that regulate and execute this process are still not fully understood. Drosophila is providing powerful new approaches for studying both the signalling pathways that activate apoptosis, and the components of the basic cell death programme. Here, we summarize progress in understanding how distinct signals influence the death of particular cells in Drosophila, and then review recent results that suggest these act through a single pathway in which the reaper gene product plays a central role.

Journal Article↗
PubMed1994

Programmed cell death in Drosophila.

During Drosophila development, large numbers of cells undergo natural cell death. Even though the onset of these deaths is controlled by many different signals, most of the dying cells undergo common morphological and biochemical changes that are characteristic of apoptosis in vertebrates. We have surveyed a large fraction of the Drosophila genome for genes that are required for programmed cell death by examining the pattern of apoptosis in embryos homozygous for previously identified chromosomal deletions. A single region on the third chromosome (in position 75C1,2) was found to be essential for all cell deaths that normally occur during Drosophila embryogenesis. We have cloned the corresponding genomic DNA and isolated a gene, reaper, which is capable of restoring apoptosis when reintroduced into cell death defective deletions. The reaper gene is specifically expressed in cells that are doomed to die, and its expression precedes the first morphological signs of apoptosis by 1-2 h. This gene is also rapidly induced upon X-ray irradiation, and reaper deletions offer significant protection against radiation-induced apoptosis. Our results suggest that reaper represents a key regulatory switch for the activation of apoptosis in response to a variety of distinct signals.

Animals↗
PubMed1994

Genetic control of programmed cell death in Drosophila.

A gene, reaper (rpr), that appears to play a central control function for the initiation of programmed cell death (apoptosis) in Drosophila was identified. Virtually all programmed cell death that normally occurs during Drosophila embryogenesis was blocked in embryos homozygous for a small deletion that includes the reaper gene. Mutant embryos contained many extra cells and failed to hatch, but many other aspects of development appeared quite normal. Deletions that include reaper also protected embryos from apoptosis caused by x-irradiation and developmental defects. However, high doses of x-rays induced some apoptosis in mutant embryos, and the resulting corpses were phagocytosed by macrophages. These data suggest that the basic cell death program is intact although it was not activated in mutant embryos. The DNA encompassed by the deletion was cloned and the reaper gene was identified on the basis of the ability of cloned DNA to restore apoptosis to cell death defective embryos in germ line transformation experiments. The reaper gene appears to encode a small peptide that shows no homology to known proteins, and reaper messenger RNA is expressed in cells destined to undergo apoptosis.

Amino Acid Sequence↗
PubMed1993

Dror, a potential neurotrophic receptor gene, encodes a Drosophila homolog of the vertebrate Ror family of Trk-related receptor tyrosine kinases.

We have identified a Drosophila gene, Dror, which encodes a putative receptor tyrosine kinase (RTK) and maps to cytological location 31B/C on the second chromosome. In embryos, this gene is expressed specifically in the developing nervous system. The Dror protein appears to be a homolog of two human RTKs, Ror1 and Ror2. Dror and Ror1 proteins share 36% amino acid identity in their extracellular domains and 61% identity in their catalytic tyrosine kinase (TK) domains. Ror1 and Ror2 were originally identified on the basis of the similarity of their TK domains to the TK domains of members of the Trk family of neurotrophin receptors. The Dror protein shows even greater similarity to the Trk proteins within this region than do the human Ror proteins. In light of its similarity to trk and its neural-specific expression pattern, we suggest that Dror may encode a neurotrophic receptor that functions during early stages of neural development in Drosophila.

Amino Acid Sequence↗
PubMed1993

Topography in the Drosophila visual system.

The Drosophila visual system offers an excellent opportunity for studying the development of proper retinotopic connections at the level of individual identifiable cell types. Recent work suggests that, despite obvious anatomical and developmental differences, at least some of the general developmental strategies operating in the Drosophila visual system parallel observations made previously for vertebrates. The extensive repertoire of powerful genetic and molecular techniques available in Drosophila can now be directed towards determining whether these parallels also reflect similarities in the underlying molecular mechanisms.

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