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G M Rubin

Publications and source records attributed to G M Rubin.

At least 91 records · Page 5Linked to original sources
PubMed1995

phyllopod functions in the fate determination of a subset of photoreceptors in Drosophila.

phyllopod (phyl) encodes a novel protein required for fate determination of photoreceptors R1, R6, and R7, the last three photoreceptors to be recruited into the ommatidia of the developing Drosophila eye. Genetic data suggests that phyl acts downstream of Ras1, raf, and yan to promote neuronal differentiation in this subset of photoreceptors. Ectopic expression of phyl in the cone cell precursors mimics the effect of ectopic activation of Ras1, suggesting that phyl expression is regulated by Ras1. phyl is also required for embryonic nervous system and sensory bristle development.

Amino Acid Sequence↗
PubMed1995

The Ras signaling pathway in Drosophila.

During Drosophila eye development, a Ras cascade mediates the decision between neuronal and non-neuronal differentiation of the R7 photoreceptor precursor. Recent genetic and molecular studies have identified a set of protein kinases as components of the Ras cascade and nuclear targets of the cascade, including Yan, Pointed, Jun, and Phyllopod. The Ras cascade functions in other Drosophila signal transduction pathways, eliciting a distinct response in each case, presumably through phosphorylation of specific transcription factors.

Animals↗
PubMed1995

A genetic analysis of the 63E-64A genomic region of Drosophila melanogaster: identification of mutations in a replication factor C subunit.

We have performed an F2 genetic screen to identify lethal mutations within the 63E-64A genomic region. We have isolated 122 mutations in 20 different complementation groups. Of these groups, 16 are represented by multiple alleles. We have also established that the Rop and Ras2 genes are located within the 63E-64A genomic domain at 64A10,11. We have sequenced 10.2 kb of DNA surrounding this gene pair and find that in addition to Rop and Ras2 there is another gene located within this DNA sequence. The gene product, which we have named Rfc40, shows 68% identity to the 40-kDa subunit of replication factor C. We find that the members of one complementation group (13 alleles) derived from our screen correspond to mutations in the Rop gene, whereas the members of another (five alleles) correspond to mutations in the Rfc40 gene. In addition we have isolated 11 new mutant alleles of the disembodied gene.

Amino Acid Sequence↗
PubMed1995

wingless inhibits morphogenetic furrow movement in the Drosophila eye disc.

Differentiation of the Drosophila eye imaginal disc is an asynchronous, repetitive process which proceeds across the disc from posterior to anterior. Its propagation correlates with the expression of decapentaplegic at the front of differentiation, in the morphogenetic furrow. Both differentiation and decapentaplegic expression are maintained by Hedgehog protein secreted by the differentiated cells posterior to the furrow. However, their initiation at the posterior margin occurs prior to hedgehog expression by an unknown mechanism. We show here that the wingless gene contributes to the correct spatial localization of initiation. Initiation of the morphogenetic furrow is restricted to the posterior margin by the presence of wingless at the lateral margins; removal of wingless allows lateral initiation. Ectopic expression of wingless at the posterior margin can also inhibit normal initiation. In addition, the presence of wingless in the center of the disc can prevent furrow progression. These effects of wingless are achieved without altering the expression of decapentaplegic.

Animals↗
PubMed1995

Shortsighted acts in the decapentaplegic pathway in Drosophila eye development and has homology to a mouse TGF-beta-responsive gene.

Differentiation in the Drosophila eye imaginal disc traverses the disc as a wave moving from posterior to anterior. The propagation of this wave is driven by hedgehog protein secreted by the differentiated cells in the posterior region of the disc. Hedgehog induces decapentaplegic expression at the front of differentiation, in the morphogenetic furrow. We have identified a gene, shortsighted, which is expressed in a hedgehog-dependent stripe in the undifferentiated cells just anterior to the furrow and which appears to be involved in the transmission of the differentiation-inducing signal; a reduction in shortsighted function leads to a delay in differentiation and to a loss of photoreceptors in the adult. shortsighted is also required for a morphogenetic movement in the brain that reorients the second optic lobe relative to the first. shortsighted encodes a cytoplasmic leucine zipper protein with homology to a mouse gene, TSC-22, which is transcriptionally induced in response to TGF-beta.

Amino Acid Sequence↗
PubMed1994

Identification of genes that interact with the sina gene in Drosophila eye development.

The sina gene encodes a nuclear protein that is required for the correct development of R7 photoreceptor cells in the Drosophila eye. We conducted a genetic screen for mutations that reduce the activity of sina and found mutations that define nine genes whose products may be required for normal sina activity. Three of these genes also appear to be essential for signaling by the Sevenless-Ras pathway in R7 cells, of which one gene corresponds to the rolled locus (rl). The rl gene is known to encode a mitogen-activated protein kinase necessary for signaling by Ras. These results suggest that the products of these three genes may participate in a signaling pathway involving both Ras and Sina, possibly by functionally linking these two proteins.

Animals↗
PubMed1994

The activities of two Ets-related transcription factors required for Drosophila eye development are modulated by the Ras/MAPK pathway.

We show that the activities of two Ets-related transcription factors required for normal eye development in Drosophila, pointed and yan, are regulated by the Ras1/MAPK pathway. The pointed gene codes for two related proteins, and we show that one form is a constitutive activator of transcription, while the activity of the other form is stimulated by the Ras1/MAPK pathway. Mutation of the single consensus MAPK phosphorylation site in the second form abrogates this responsiveness. yan is a negative regulator of photoreceptor determination, and genetic data suggest that it acts as an antagonist of Ras1. We demonstrate that yan can repress transcription and that this repression activity is negatively regulated by the Ras1/MAPK signal, most likely through direct phosphorylation of yan by MAPK.

Animals↗
PubMed1994

The Drosophila melanogaster ribosomal S6 kinase II-encoding sequence.

A cDNA encoding the Drosophila melanogaster p90 ribosomal S6 kinase II (RSK) was isolated from an eye-antennal imaginal disc library and sequenced. The conceptually translated protein is 60-63% identical to vertebrate RSK homologs and contains a perfectly conserved mitogen-activated protein kinase phosphorylation site. The gene was mapped to the base of the X chromosome in division 20 by in situ hybridization to polytene chromosomes.

Amino Acid Sequence↗
PubMed1994

Mutations in Hsp83 and cdc37 impair signaling by the sevenless receptor tyrosine kinase in Drosophila.

A highly conserved signal cascade functions subsequent to receptor tyrosine kinase activation. Signaling by the sevenless receptor, required for differentiation of the R7 photoreceptor neuron in Drosophila, is reduced by mutations in E(sev)3A and E(sev)3B. We show here that E(sev)3A is a member of the Hsp90 family of stress proteins and that E(sev)3B encodes a homolog of the cell cycle control protein Cdc37 from S. cerevisiae. Mutations in E(sev)3B also dominantly enhance mutations in Dmcdc2, the gene encoding the p34 protein kinase that regulates the G2/M transition. Together, these data support a role for Hsp90 proteins in tyrosine kinase regulation and suggest that signals promoting neuronal differentiation may involve cell cycle control.

Amino Acid Sequence↗
PubMed1994

The Drosophila peanut gene is required for cytokinesis and encodes a protein similar to yeast putative bud neck filament proteins.

We have identified a Drosophila gene, peanut (pnut), that is related in sequence to the CDC3, CDC10, CDC11, and CDC12 genes of S. cerevisiae. These genes are required for cytokinesis, and their products are present at the bud neck during cell division. We find that pnut is also required for cytokinesis: in pnut mutants, imaginal tissues fail to proliferate and instead develop clusters of large, multinucleate cells. Pnut protein is localized to the cleavage furrow of dividing cells during cytokinesis and to the intercellular bridge connecting postmitotic daughter cells. In addition to its role in cytokinesis, pnut displays genetic interactions with seven in absentia, a gene required for neuronal fate determination in the compound eye, suggesting that pnut may have pleiotropic functions. Our results suggest that this class of proteins is involved in aspects of cytokinesis that have been conserved between flies and yeast.

Amino Acid Sequence↗
PubMed1994

Mutations in the Drosophila Rop gene suggest a function in general secretion and synaptic transmission.

The Drosophila protein Rop shows similarity with the Sec1p protein of S. cerevisiae. Sec1p has an essential role in secretion, whereas most related proteins from higher organisms are hypothesized to function in neurotransmitter release. We show that, like the latter proteins, Rop is expressed in the nervous system, but it is expressed in other tissues as well, many of which are actively engaged in secretion. We have isolated mutations in the Rop gene and find that the extracellular accumulation of a number of normally secreted cellular products fails to occur in null mutant animals, which subsequently die at a late embryonic stage. Electrophysiological recordings on temperature-sensitive Rop mutants show that reductions in Rop activity result in a loss of the normal synaptic response to a light stimulus. These data suggest that a member of the Sec1p class of proteins has an in vivo function in both general secretion and synaptic transmission.

Amino Acid Sequence↗
PubMed1994

The C-terminus of the homeodomain is required for functional specificity of the Drosophila rough gene.

In contrast to most Drosophila homeobox genes, which are required during embryogenesis, the rough gene is involved in photoreceptor cell specification in the compound eye. Taking advantage of the viability of null rough alleles and the small size of the rough gene, we have combined in vivo and in vitro mutagenesis to define important functional domains in the rough protein. All missense mutations found to disrupt rough function mapped to highly conserved amino acids in the homeodomain (HD), suggesting that the nature of few, if any, single amino acids outside the HD is critical for rough activity. The analysis of chimeric proteins, in which the whole HD or parts of it were swapped between the rough and Antennapedia (Antp) proteins, revealed that the C-terminus of the rough HD is important for rough activity in vivo. This C-terminal region was also found to be required for the recognition of rough binding sites in vitro. Our data suggest that amino acids located in the C-terminus of the homeodomain may play important roles in selective binding site recognition.

Alleles↗
PubMed1994

dachshund encodes a nuclear protein required for normal eye and leg development in Drosophila.

Neural specification and differentiation in the Drosophila eye sweep across the unpatterned epithelial monolayer of the eye imaginal disc following a developmental wave termed the morphogenetic furrow. The furrow begins at the posterior margin of the eye imaginal disc and moves anteriorly as a linear front. Progression of the furrow requires the function of hedgehog, which encodes a secreted signaling protein. We characterize mutations in dachshund, a gene that encodes a novel nuclear protein required for normal cell-fate determination of imaginal disc cells. In the absence of dachshund function, cells at the posterior margin of the eye disc fail to follow a retinal differentiation pathway and appear to adopt a cuticle fate instead. These cells are therefore unable to respond to pattern propagation signals such as hedgehog and furrow initiation does not occur. In contrast, cells in more anterior portions of the eye disc are able to differentiate as retinal cells in the absence of dachshund activity and respond normally to patterning signals. These results suggest that posterior margin cells are distinct from other cells of the eye imaginal disc by early stages of development. dachshund is also necessary for proper differentiation of a subset of segments in the developing leg. Null mutations in dachshund result in flies with no eyes and shortened legs.

Amino Acid Sequence↗
PubMed1994

Expression of baculovirus P35 prevents cell death in Drosophila.

The baculovirus P35 protein functions to prevent apoptotic death of infected cells. We have expressed P35 in the developing embryo and eye of the fly Drosophila melanogaster. P35 eliminates most, if not all, normally occurring cell death in these tissues, as well as X-irradiation-induced death. Excess pupal eye cells that are normally eliminated by apoptosis develop into pigment cells when their death is prevented by P35 expression. Our results suggest that one mechanism by which viruses prevent the death of the host cell is to block a cell death pathway that mediates normally occurring cell death. Identification of molecules that interact biochemically or genetically with P35 in Drosophila should provide important insights into how cell death is regulated.

Animals↗
PubMed1993

The TGF beta homolog dpp and the segment polarity gene hedgehog are required for propagation of a morphogenetic wave in the Drosophila retina.

Development of the Drosophila retina occurs asynchronously; differentiation, its front marked by the morphogenetic furrow, progresses across the eye disc epithelium over a 2 day period. We have investigated the mechanism by which this front advances, and our results suggest that developing retinal cells drive the progression of morphogenesis utilizing the products of the hedgehog (hh) and decapentaplegic (dpp) genes. Analysis of hh and dpp genetic mosaics indicates that the products of these genes act as diffusible signals in this process. Expression of dpp in the morphogenetic furrow is closely correlated with the progression of the furrow under a variety of conditions. We show that hh, synthesized by differentiating cells, induces the expression of dpp, which appears to be a primary mediator of furrow movement.

Animals↗
PubMed1993

The interaction of bride of sevenless with sevenless is conserved between Drosophila virilis and Drosophila melanogaster.

An inductive interaction between the sevenless (sev) transmembrane tyrosine kinase receptor and the bride of sevenless (boss) transmembrane ligand is required for the development of the R7 photoreceptor neuron in the compound eye of Drosophila melanogaster. The boss protein is proposed to contain a large N-terminal extracellular domain, seven transmembrane segments, and a C-terminal cytoplasmic tail. The boss protein from Drosophila virilis (bossvir) retains strong amino acid identity with loss from D. melanogaster (bossmel): 73% identity in the N-terminal extracellular domain and 91% identity in the seven-transmembrane domain, including the cytoplasmic tail. By using P-element-mediated DNA transformation, the bossmel and bossvir genes were shown to rescue the D. melanogaster boss1 mutation. The expression of bossvir protein in D. melanogaster is indistinguishable from that of bossmel protein. Noncoding sequences which may regulate boss expression were identified based on their conservation during evolution. The predicted sev protein from D. virilis (sevvir) was previously shown to be 63% identical to sev from D. melanogaster (sevmel). A chimeric gene, (sevvir/mel), encoding the extracellular domain of sevvir and the cytoplasmic domain of sevmel rescues the D. melanogaster sevd2 mutation through interaction with either bossvir or bossmel.

Amino Acid Sequence↗