Segregation of the somatic and germ-cell pathways of development in Drosophila

Two groups of lethal mutations that are expressed only in somatic cells were isolated using the gonosomic selective method. The mutations tend to be organized in clusters along the sex chromosome. Analysis of mutation expression allowed to characterize the degree of changes in genetic diversity of somatic and germ lines in development; it is minimal in the III instar larvae and prepupae and maximal in the I and II instar larvae and pupae.     

Connecting cell-cycle activation to neurodegeneration in Drosophila

Studies in cell-culture systems and in postmortem tissue from human disease have suggested a connection between cell-cycle activation and neurodegeneration. The fruit fly Drosophila melanogaster has recently emerged as a powerful model system in which to model neurodegenerative diseases. Here we review work in the fly that has begun to address some of the important questions regarding the relationship between cell-cycle activation and neurodegeneration in vivo, including recent data implicating cell-cycle activation as a downstream effector of tau-induced neurodegeneration. We suggest how powerful research tools in Drosophila might be utilized to approach fundamental questions that remain.     

Localized activation of RTK/MAPK pathways during Drosophila development

Receptor tyrosine kinase (RTK) signaling is mediated by a signaling cascade culminating in activation of mitogen-activated protein kinase (MAPK) by double phosphorylation on threonine and tyrosine residues. The pattern of MAPK activation can now be directly visualized in situ during embryonic and adult development using an antiserum is specific for the double phosphorylated form of MAPK (db-P MAPK).^1,2 The pattern of MAPK activation detected by this antiserum in developing embryos and larval imaginal discs conforms remarkably well to the inferred pattern of known RTK function. In addition, db-P MAPK staining directly reveals features of signaling such as the range of signal spreading and the kinetics of RTK activation, which would be difficult to measure by other methods. The ability to visualize the output of RTK signaling also permits detailed establishment of epistatic relationships between signaling components of RTK cascades. BioEssays 20 :189–194, 1998.© 1998 John Wiley & Sons, Inc.     

Drosophila neural pathways

Summary TheDrosophila giant axon pathways cervical connective — thoracic indirect flight muscles were studied by a combined electrophysiological and genetic analysis. A functional coupling of the left and right giant axon pathways was revealed by intracellular recordings of electrical responses of the thoracic indirect flight muscles, when evoked by electrical stimulation of cervical connective (Fig. 2). This functional coupling was demonstrated in wild-type flies and in flies of the single gene, temperature-sensitive paralytic mutation,para ^ts . The functional coupling was evident also in selected bilateral gynandromorph flies, mosaics for thepara ^ts mutation (Fig. 1), even at restricted elevated ambient temperature (Tables 1–3). Analysis of neurally evoked electrogenic muscle responses of wild-type flies, following injection of picrotoxin, verifies the notion that both the dorsoventral and the dorsolongitudinal flight muscles share a common activating pathway (Fig. 3). Picrotoxin application to gynandromorph flies demonstrated the existence of neuronal elements additional to the giant axon pathways, that evoke the indirect flight muscles in response to cervical stimulation (Figs. 4, 5). An unexpected finding was the poor correlation between the mosaic external phenotype of the gynandromorph flies ofpara ^ts mutation and the genotype of neural pathways activating their thoracic flight muscles, as evidenced by the intracellular recordings.Abbreviations GA giant axon - DVM dorsoventral muscle - DLM dorsolongitudinal muscle - PSI peripherally synapsing interneuron - ts temperature sensitive     

Multiple signaling pathways and a selector protein sequentially regulate Drosophila wing development

Drosophila wing development is a useful model to study organogenesis, which requires the input of selector genes that specify the identity of various morphogenetic fields (Weatherbee, S. D. and Carroll, S. B. (1999) Cell 97, 283-286) and cell signaling molecules. In order to understand how the integration of multiple signaling pathways and selector proteins can be achieved during wing development, we studied the regulatory network that controls the expression of Serrate (Ser), a ligand for the Notch (N) signaling pathway, which is essential for the development of the Drosophila wing, as well as vertebrate limbs. Here, we show that a 794 bp cis-regulatory element located in the 3' region of the Ser gene can recapitulate the dynamic patterns of endogenous Ser expression during wing development. Using this enhancer element, we demonstrate that Apterous (Ap, a selector protein), and the Notch and Wingless (Wg) signaling pathways, can sequentially control wing development through direct regulation of Ser expression in early, mid and late third instar stages, respectively. In addition, we show that later Ser expression in the presumptive vein cells is controlled by the Egfr pathway. Thus, a cis-regulatory element is sequentially regulated by multiple signaling pathways and a selector protein during Drosophila wing development. Such a mechanism is possibly conserved in the appendage outgrowth of other arthropods and vertebrates.     

Modulation of AP and DV signaling pathways by the homeotic gene Ultrabithorax during haltere development in Drosophila

Suppression of wing fate and specification of haltere fate in Drosophila by the homeotic gene Ultrabithorax is a classical example of Hox regulation of serial homology (Lewis, E.B. 1978. Nature 276, 565-570) and has served as a paradigm for understanding homeotic gene function. We have used DNA microarray analyses to identify potential targets of Ultrabithorax function during haltere specification. Expression patterns of 18 validated target genes and functional analyses of a subset of these genes suggest that down-regulation of both anterior-posterior and dorso-ventral signaling is critical for haltere fate specification. This is further confirmed by the observation that combined over-expression of Decapentaplegic and Vestigial is sufficient to override the effect of Ubx and cause dramatic haltere-to-wing transformations. Our results also demonstrate that analysis of the differential development of wing and haltere is a good assay system to identify novel regulators of key signaling pathways.     

Overexpression of ubiquitin carboxyl terminal hydrolase impairs multiple pathways during eye development in Drosophila melanogaster

UCH-L1 (ubiquitin carboxyl terminal hydrolase L1) is well known as an enzyme that hydrolyzes polyubiquitin at its C-terminal to release ubiquitin monomers. Although the overexpression of UCH-L1 inhibits proteasome activity in cultured cells, its biological significance in living organisms has not been clarified in detail. Here, we utilized Drosophila as a model system to examine the effects of the overexpression of dUCH, a Drosophila homologue of UCH-L1, on development. Overexpression in the eye imaginal discs induced a rough eye phenotype in the adult, at least partly resulting from the induction of caspase-dependent apoptosis followed by compensatory proliferation. Genetic crosses with enhancer trap lines marking the photoreceptor cells also revealed that the overexpression of dUCH specifically impaired R7 photoreceptor cell differentiation with a reduction in activated extracellular-signal-regulated kinase signals. Furthermore, the dUCH-induced rough eye phenotype was rescued by co-expression of the sevenless gene or the Draf gene, a downstream component of the mitogen-activated protein kinase (MAPK) cascade. These results indicate that the overexpression of dUCH impairs R7 photoreceptor cell differentiation by down-regulating the MAPK pathway. Interestingly, this process appears to be independent of its pro-apoptotic function.     

Adaptive evolution of metabolic pathways in Drosophila

The adaptive significance of enzyme variation has been of central interest in population genetics. Yet, how natural selection operates on enzymes in the larger context of biochemical pathways has not been broadly explored. A basic expectation is that natural selection on metabolic phenotypes will target enzymes that control metabolic flux, but how adaptive variation is distributed among enzymes in metabolic networks is poorly understood. Here, we use population genetic methods to identify enzymes responding to adaptive selection in the pathways of central metabolism in Drosophila melanogaster and Drosophila simulans. We report polymorphism and divergence data for 17 genes that encode enzymes of 5 metabolic pathways that converge at glucose-6-phosphate (G6P). Deviations from neutral expectations were observed at five loci. Of the 10 genes that encode the enzymes of glycolysis, only aldolase (Ald) deviated from neutrality. The other 4 genes that were inconsistent with neutral evolution (glucose-6-phosphate dehydrogenase [G6pd]), phosphoglucomutase [Pgm], trehalose-6-phosphate synthetase [Tps1], and glucose-6phosphatase [G6pase] encode G6P branch point enzymes that catalyze reactions at the entry point to the pentose-phosphate, glycogenic, trehalose synthesis, and gluconeogenic pathways. We reconcile these results with population genetics theory and existing arguments on metabolic regulation and propose that the incidence of adaptive selection in this system is related to the distribution of flux control. The data suggest that adaptive evolution of G6P branch point enzymes may have special significance in metabolic adaptation.     

Neuronal development in the Drosophila retina

Nervous systems of higher organisms are comprised of a variety of cell types which are interconnected in a precise manner. The molecular mechanisms that lead to the specification of neuronal cell types are not well understood. The compound eye of the fruit fly Drosophila is an attractive experimental system to understand these mechanism. The compound eye is a reiterated neural pattern with several hundred unit structures and is amenable to both classical and molecular genetic methods. During the development of the compound eye cell–cell interactions and positional information play a critical role in the determination of cell fate. Recent genetic and molecular studies have provided important clues regarding the nature of the molecules involved in cellular signalling and neuronal differentiation. © 1993 John Wiley & Sons, Inc.     

Connecting recombination,nucleotide diversity,and species divergence in Drosophila

The association between recombination rate and nucleotide diversity provides compelling evidence for the action of natural selection across much of the Drosophila melanogaster genome. This conclusion is further supported by the lack of association between recombination rate and nucleotide divergence between species. However, studies of other species, including other Drosophila, have not always yielded the same results. Our recent study measured these parameters within the D. pseudoobscura species group using next-generation sequencing and high-throughput genotyping technologies. We documented fine-scale variation in crossover rate within D. pseudoobscura, and we observed that crossover variation was strongly associated with nucleotide diversity only when measured at a fine-scale. We also observed associations between crossover rate and sequence differences between D. pseudoobscura and its close relatives. These latter associations could have been driven in part by mutagenic effects associated with double-strand break repair, but we cannot exclude the possibility that it results primarily from shared ancestral polymorphisms. Overall, this work strongly underscores the importance of scale in testing for associations of recombination rate with other parameters, and it brings us one small step closer to understanding the role of natural selection and other evolutionary forces in shaping divergence among genomes.     

Heart development in Drosophila

The Drosophila heart, also called the dorsal vessel, is an organ for hemolymph circulation that resembles the vertebrate heart at its transient linear tube stage. Dorsal vessel morphogenesis shares several similarities with early events of vertebrate heart development and has proven to be an insightful system for the study of cardiogenesis due to its relatively simple structure and the productive use of Drosophila genetic approaches. In this review, we summarize published findings on Drosophila heart development in terms of the regulators and genetic pathways required for cardiac cell specification and differentiation, and organ formation and function. Emerging genome-based strategies should further facilitate the use of Drosophila as an advantageous system in which to identify previously unknown genes and regulatory networks essential for normal cardiac development and function.     

Integration of chemosensory pathways in the Drosophila second-order olfactory centers

BACKGROUND: Behavioral responses to odorants require neurons of the higher olfactory centers to integrate signals detected by different chemosensory neurons. Recent studies revealed stereotypic arborizations of second-order olfactory neurons from the primary olfactory center to the secondary centers, but how third-order neurons read this odor map remained unknown. RESULTS: Using the Drosophila brain as a model system, we analyzed the connectivity patterns between second-order and third-order olfactory neurons. We first isolated three common projection zones in the two secondary centers, the mushroom body (MB) and the lateral horn (LH). Each zone receives converged information via second-order neurons from particular subgroups of antennal-lobe glomeruli. In the MB, third-order neurons extend their dendrites across various combinations of these zones, and axons of this heterogeneous population of neurons converge in the output region of the MB. In contrast, arborizations of the third-order neurons in the LH are constrained within a zone. Moreover, different zones of the LH are linked with different brain areas and form preferential associations between distinct subsets of antennal-lobe glomeruli and higher brain regions. CONCLUSIONS: MB is known to be an indispensable site for olfactory learning and memory, whereas LH function is reported to be sufficient for mediating direct nonassociative responses to odors. The structural organization of second-order and third-order neurons suggests that MB is capable of integrating a wide range of odorant information across glomeruli, whereas relatively little integration between different subsets of the olfactory signal repertoire is likely to occur in the LH.     

Pre-existing neuronal pathways in the developing optic lobes of Drosophila

We have identified a set of larval neurones in the developing adult optic lobes of Drosophila by selectively labelling cells that have undergone only a few mitoses. A cluster of three cells is located in each of the optic lobes near the insertion site of the optic stalk. Their axons fasciculate with fibres of the larval optic nerve, the Bolwig's nerve, and then form part of the posterior optic tract. These cells are likely to be first order interneurones of the larval visual system. Unlike the Bolwig's nerve, they persist into the adult stage. The possibility of a pioneering function of the larval visual system during formation of the adult optic lobe neuropil is discussed.     

Sensory neurons and peripheral pathways in Drosophila embryos

Summary The thoracic and abdominal segments of the Drosophila embryo contain 373 neurons innervating external sensory structures and 162 neurons innervating chordotonal organs. These neurons are arranged in ventral, lateral and dorsal clusters within each segment, in a highly invariant pattern. Two fascicles are formed in each segment as the sensory axons grow ventrally towards the CNS and meet motor axons growing dorsally from the CNS. In all but the last segment, the anterior fascicle is contributed by the dorsal and lateral neurons, while the posterior one is formed by the ventral neurons. Five distinct segmental patterns are described, corresponding to (1) the prothorax, (2) the other two thoracic segments, (3) the first seven abdominal segments, (4) the eighth and (5) the ninth (and possibly the tenth) abdominal segments.The publisher regrets that two companion papers unfortunately were published out of sequence. The present paper should have preceded the paper entitled The sense organs in the Drosophila larva and their relation to the embryonic pattern of sensory neurons, which appeared in Volume 195, Number 4 of the journal (pp 222–228)