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U Gaul

Publications and source records attributed to U Gaul.

At least 19 recordsLinked to original sources
PubMed2001

A novel muscle LIM-only protein is generated from the paxillin gene locus in Drosophila.

Paxillin is a protein containing four LIM domains, and functions in integrin signaling. We report here that two transcripts are generated from the paxillin gene locus in Drosophila; one encodes a protein homolog of the vertebrate Paxillin (DPxn37), and the other a protein with only three LIM domains, partly encoded by its own specific exon (PDLP). At the myotendinous junctions of Drosophila embryos where integrins play important roles, both DPxn37 and PDLP are highly expressed with different patterns; DPxn37 is predominantly concentrated at the center of the junctions, whereas PDLP is highly enriched at neighboring sides of the junction centers, primarily expressed in the mesodermal myotubes. Northern blot analysis revealed that DPxn37 is ubiquitously expressed throughout the life cycle, whereas PDLP expression exhibits a biphasic pattern during development, largely concomitant with muscle generation and remodeling. Our results collectively reveal that a unique system exists in Drosophila for the generation of a novel type of LIM-only protein, highly expressed in the embryonic musculature, largely utilizing the Paxillin LIM domains.

3T3 Cells↗
PubMed2001

Dpp and Hedgehog mediate neuron-glia interactions in Drosophila eye development by promoting the proliferation and motility of subretinal glia.

Neuron-glia interactions are crucial for the establishment of normal connectivity in the nervous system during development, but the molecular signals involved in these interactions are largely unknown. Here we show that differentiating photoreceptors in the developing Drosophila eye influence the proliferative and migratory behavior of the subretinal glia through the diffusible factors Decapentaplegic (Dpp) and Hedgehog (Hh). We demonstrate that proliferation and migration of the glia are separable processes, and that Dpp promotes both the proliferation and motility of the glia, whereas Hh appears to promote only their motility; neither specifies the direction of migration. We present evidence that Dpp and Hh act on the glia in parallel and through the regulation of transcription. Finally, we show that ectopic migration of subretinal glia can result in the ectopic projection of photoreceptor axons. Our study suggests a novel function for Hh in regulating migratory behavior and provides further evidence for a complex mutual dependence between glial and neuronal cells during development.

Animals↗
PubMed2000

The Drosophila gene abstrakt, required for visual system development, encodes a putative RNA helicase of the DEAD box protein family.

The molecular mechanisms underlying axonal pathfinding are not well understood. In a genetic screen for mutations affecting the projection of the larval optic nerve we isolated the abstrakt locus. abstrakt is required for pathfinding of the larval optic nerve, and it also affects development in both the adult visual system and the embryonic CNS. Here we report the molecular characterization of abstrakt. It encodes a putative ATP-dependent RNA helicase of the DEAD box protein family, with two rare substitutions in the PTRELA and the RG-D motifs, thought to be involved in oligonucleotide binding: serine for threonine, and lysine for arginine, respectively. Two mutant alleles of abstrakt show amino acid exchanges in highly conserved positions. A glycine to serine exchange in the HRIGR motif, which is involved in RNA binding and ATP hydrolysis, results in a complete loss of protein function; and a proline to leucine exchange located between the highly conserved ATPase A and PTRELA motifs results in temperature-sensitive protein function. Both the broad requirement for abstrakt gene function and its ubiquitous expression are consistent with a molecular function of the abstrakt protein in mRNA splicing or translational control.

Alleles↗
PubMed1999

Activation of the Drosophila C3G leads to cell fate changes and overproliferation during development, mediated by the RAS-MAPK pathway and RAP1.

The cellular signal transduction pathways by which C3G, a RAS family guanine nucleotide exchange factor, mediates v-crk transformation are not well understood. Here we report the identification of Drosophila C3G, which, like its human cognate, specifically binds to CRK but not DRK/GRB2 adaptor molecules. During Drosophila development, constitutive membrane binding of C3G, which also occurs during v-crk transformation, results in cell fate changes and overproliferation, mimicking overactivity of the RAS-MAPK pathway. The effects of C3G overactivity can be suppressed by reducing the gene dose of components of the RAS-MAPK pathway and of RAP1. These findings provide the first in vivo evidence that membrane localization of C3G can trigger activation of RAP1 and RAS resulting in the activation of MAPK, one of the hallmarks of v-crk transformation previously thought to be mediated through activation of SOS.

Amino Acid Sequence↗
PubMed1999

In vivo functional analysis of Drosophila Gap1: involvement of Ca2+ and IP4 regulation.

Control of Ras activity is crucial for normal cellular behavior such as fate determination during development. Although several GTPase activating proteins (GAPs) have been shown to act as negative regulators of Ras, the mechanisms involved in regulating their activity in vivo are poorly understood. Here we report the structural requirements for Gap1 activity in cone cell fate decisions during Drosophila eye development. The Gap1 catalytic domain alone is not sufficient for in vivo activity, indicating a requirement for the additional domains. An inositol-1,3,4, 5-tetrakisphosphate (IP4)-sensitive extended PH domain is essential for Gap1 activity, while Ca2+-sensitive C2 domains and a glutamine-rich region contribute equally to full activity in vivo. Furthermore, we find a strong positive genetic interaction between Gap1 and phospholipase Cgamma (PLCgamma), an enzyme which generates inositol-1,4,5-trisphosphate, a precursor for IP4 and a second messenger for intracellular Ca2+ release. These results suggest that Gap1 activity in vivo is stimulated under conditions of elevated intracellular Ca2+ and IP4. Since receptor tyrosine kinases (RTKs) trigger an increase in intracellular Ca2+ and IP4 concentration through stimulation of PLCgamma, RTKs may stimulate not only activation of Ras but also its deactivation by Gap1, thereby moderating the strength and duration of the Ras signal.

Amino Acids↗
PubMed1999

A methionine aminopeptidase and putative regulator of translation initiation is required for cell growth and patterning in Drosophila.

We have isolated mutations in the gene Drosophila methionine aminopeptidase 2 (DMAP2), which encodes a homolog of the type 2 methionine aminopeptidase from yeast, also known as the eukaryotic initiation factor 2alpha (eIF2alpha) associated protein p67. Weak DMAP2 mutations cause ommatidial rotation defects and loss of ventral tissue in the compound eye as well as extra wing veins, whereas stronger alleles impair tissue growth. These limited phenotypes, in conjunction with the differential accumulation of DMAP2 transcripts throughout embryonic and larval development, suggest that a subset of proteins is spatially and temporally regulated at the level of post-translational processing or translation initiation during development. These results provide genetic evidence for post-transcriptional control in the development of multicellular organisms.

Amino Acid Sequence↗
PubMed1999

Migration and function of glia in the developing Drosophila eye.

Although glial cells have been implicated widely in the formation of axon tracts in both insects and vertebrates, their specific function appears to be context-dependent, ranging from providing essential guidance cues to playing a merely facilitory role. Here we examine the role of the retinal basal glia (RBG) in photoreceptor axon guidance in Drosophila. The RBG originate in the optic stalk and have been thought to migrate into the eye disc along photoreceptor axons, thus precluding any role in axon guidance. Here we show the following. (1) The RBG can, in fact, migrate into the eye disc even in the absence of photoreceptor axons in the optic stalk; they also migrate to ectopic patches of differentiating photoreceptors without axons providing a continuous physical substratum. This suggests that glial cells are attracted into the eye disc not through haptotaxis along established axons, but through another mechanism, possibly chemotaxis. (2) If no glial cells are present in the eye disc, photoreceptor axons are able to grow and direct their growth posteriorly as in wild type, but are unable to enter the optic stalk. This indicates that the RBG have a crucial role in axon guidance, but not in axonal outgrowth per se. (3) A few glia close to the entry of the optic stalk suffice to guide the axons into the stalk, suggesting that glia instruct axons by local interaction.

Animals↗
PubMed1999

The netrin receptor frazzled is required in the target for establishment of retinal projections in the Drosophila visual system.

Retinal axons in Drosophila make precise topographic connections with their target cells in the optic lobe. Here we investigate the role of the Netrins and their receptor Frazzled in the establishment of retinal projections. We find that the Netrins, although expressed in the target, are not required for retinal projections. Surprisingly, Frazzled, found on both retinal fibers and target cells, is required in the target for attracting retinal fibers, while playing at best a redundant role in the retinal fibers themselves; this finding demonstrates that target attraction is necessary for topographic map formation. Finally, we show that Frazzled is not required for the differentiation of cells in the target. Our data suggest that Frazzled does not function as a Netrin receptor in attracting retinal fibers to the target; nor does it seem to act as a homotypic cell adhesion molecule. We favor the possibility that Frazzled in the target interacts with a component on the surface of retinal fibers, possibly another Netrin receptor.

Animals↗
PubMed1997

The genetics of visual system development in Drosophila: specification, connectivity and asymmetry.

Encoding visual information requires a complex neuronal network. Recently, genes regulating early tissue specification, the growth of retinal target structures, the connectivity of photoreceptor axons, and mirror-image retinal symmetry in Drosophila have been identified. The insights gained from studying visual system development in flies promise to inform our understanding of similar processes in vertebrates.

Animals↗
PubMed1997

Genetic analysis of the larval optic nerve projection in Drosophila.

The Drosophila larval optic nerve, called Bolwig's nerve (BN), projects into the central brain along a simple invariant path. The growth of the BN proceeds in three phases, during which the nerve changes direction at two intermediate targets, P1 and P2. Here we show that the projection of the BN is amenable to genetic dissection. In a mutagenesis screen, we have isolated mutations in 13 genes that disrupt the BN projection in distinct phases of its development. The mutant phenotypes in combination with the expression patterns of corresponding candidate genes define cellular components necessary for directing the growth of the BN toward P2 and for redirecting its growth at P2, and reveal developmental strategies employed in the establishment of the BN projection.

Alleles↗
PubMed1993

Identification of ras targets using a genetic approach.

The Sevenless receptor tyrosine kinase is required for the development of the R7 photoreceptor cell in the Drosophila eye. Several components of the Sevenless signal transduction pathway have been identified in genetic screens for enhancers/suppressors of the sevenless phenotype. These studies suggest that activation of Sevenless leads to stimulation of Ras1 activity, whereas Gap1 appears to act as a negative regulator of the pathway. Inactivation of the Gap1 locus causes transformation of non-neuronal cone cells into supernumerary R7 cells. This same mutant phenotype is observed when activated Ras1 is expressed under the control of the sevenless promoter. While studies in other organisms have demonstrated a role for ras gene products in signal transduction, the effectors of Ras activity have not yet been identified. We are carrying out genetic screens for enhancers and suppressors of the Gap1 and activated Ras1 phenotypes in the hope of identifying genes encoding some of these effectors. We are conducting chemical mutagenesis screens and have also screened existing collections of P element lines. A molecular characterization of the most promising mutations is in progress.

Animals↗
PubMed1992

A putative Ras GTPase activating protein acts as a negative regulator of signaling by the Sevenless receptor tyrosine kinase.

A Drosophila gene with similarity to the mammalian Ras GTPase activating protein has been isolated in screens for mutations that affect eye development. Inactivation of the locus, Gap1, mimics constitutive activation of the Sevenless receptor tyrosine kinase and eliminates the need for a functional Sevenless protein in the R7 cell. Our results suggest that Gap1 acts as a negative regulator of signaling by Sevenless by down-regulating the activity of the Ras1 protein, which has been shown to be a key element in signaling by Sevenless.

Amino Acid Sequence↗
PubMed1990

Regulation of Krüppel expression in the anlage of the Malpighian tubules in the Drosophila embryo.

The expression of most Drosophila segmentation genes is not limited to the early blastoderm stage, when the segmental anlagen are determined. Rather, these genes are often expressed in a variety of organs and tissues at later stages of development. In contrast to the early expression, little is known about the regulatory interactions that govern the later expression patterns. Among other tissues, the central gap gene Krüppel is expressed and required in the anlage of the Malpighian tubules at the posterior terminus of the embryo. We have studied the interactions of Krüppel with other terminal genes. The gap genes tailless and huckebein, which repress Krüppel in the central segmentation domain, activate Krüppel expression in the posterior Malpighian tubule domain. The opposite effect on the posterior Krüppel expression is achieved by the interposition of another factor, the homeotic gene fork head, which is not involved in the control of the central domain. In addition, Krüppel activates different genes in the Malpighian tubules than in the central domain. Thus, both the regulation and the function of Krüppel in the Malpighian tubules differ strikingly from its role in segmentation.

Animals↗
PubMed1989

[Pattern formation in Drosophila].

Drosophila proved an excellent system to study molecular processes in establishing the body pattern of an embryo. Genes which are active during oogenesis provide localized cues which regulate a cascade of zygotic genes that determines the developmental fate of the blastoderm cells along the longitudinal axis of the embryo.

Animals↗