Drosophila fasciclinII (fasII) mutants perform poorly after olfactory conditioning due to a defect in encoding, stabilizing, or retrieving short-term memories. Performance was rescued by inducing the expression of a normal transgene just before training and immediate testing. Induction after training but before testing failed to rescue performance, showing that Fas II does not have an exclusive role in memory retrieval processes. The stability of odor memories in fasII mutants are indistinguishable from control animals when initial performance is normalized. Like several other mutants deficient in odor learning, fasII mutants exhibit a heightened sensitivity to ethanol vapors. A combination of behavioral and genetic strategies have therefore revealed a role for Fas II in the molecular operations of encoding short-term odor memories and conferring alcohol sensitivity. The preferential expression of Fas II in the axons of mushroom body neurons furthermore suggests that short-term odor memories are formed in these neurites.

Flies, like all animals that depend on vision to navigate through the world, must integrate the optic flow created by self-motion with the images generated by prominent features in their environment. Although much is known about the responses of Drosophila melanogaster to rotating flow fields, their reactions to the more complex patterns of motion that occur as they translate through the world are not well understood. In the present study we explore the interactions between two visual reflexes in Drosophila: object fixation and expansion avoidance. As a fly flies forward, it encounters an expanding visual flow field. However, recent results have demonstrated that Drosophila strongly turn away from patterns of expansion. Given the strength of this reflex, it is difficult to explain how flies make forward progress through a visual landscape. This paradox is partially resolved by the finding reported here that when undergoing flight directed towards a conspicuous object, Drosophila will tolerate a level of expansion that would otherwise induce avoidance. This navigation strategy allows flies to fly straight when orienting towards prominent visual features.

In the March 24 issue of Science, a flurry of papers report on the impending completion of the Drosophila melanogaster genome sequence. This historic achievement is the result of a unique collaboration between the Berkeley Drosophila Genome Project (BDGP), led by Gerry Rubin, and the genomics company Celera, headed by Craig Venter. With its genome almost completely sequenced ahead of schedule, Drosophila is another important model organism to enter the postgenomic age, and represents the largest genome sequenced to date.

Germ granules, specialized ribonucleoprotein particles, are a hallmark of all germ cells. In Drosophila, an estimated 200 mRNAs are enriched in the germ plasm, and some of these have important, often conserved roles in germ cell formation, specification, survival and migration. How mRNAs are spatially distributed within a germ granule and whether their position defines functional properties is unclear. Here we show, using single-molecule FISH and structured illumination microscopy, a super-resolution approach, that mRNAs are spatially organized within the granule whereas core germ plasm proteins are distributed evenly throughout the granule. Multiple copies of single mRNAs organize into 'homotypic clusters' that occupy defined positions within the center or periphery of the granule. This organization, which is maintained during embryogenesis and independent of the translational or degradation activity of mRNAs, reveals new regulatory mechanisms for germ plasm mRNAs that may be applicable to other mRNA granules.

Gustatory sensory neurons detect caloric and harmful compounds in potential food and convey this information to the brain to inform feeding decisions. To examine the signals that gustatory neurons transmit and receive, we reconstructed gustatory axons and their synaptic sites in the adult brain, utilizing a whole-brain electron microscopy volume. We reconstructed 87 gustatory projections from the proboscis labellum in the right hemisphere and 57 from the left, representing the majority of labellar gustatory axons. Gustatory neurons contain a nearly equal number of interspersed pre- and postsynaptic sites, with extensive synaptic connectivity among gustatory axons. Morphology- and connectivity-based clustering revealed six distinct groups, likely representing neurons recognizing different taste modalities. The vast majority of synaptic connections are between neurons of the same group. This study resolves the anatomy of labellar gustatory projections, reveals that gustatory projections are segregated based on taste modality, and uncovers synaptic connections that may alter the transmission of gustatory signals.

Apoptotic cell death is a mechanism by which organisms eliminate superfluous or harmful cells. Expression of the cell death regulatory protein REAPER (RPR) in the developing Drosophila eye results in a small eye owing to excess cell death. We show that mutations in thread (th) are dominant enhancers of RPR-induced cell death and that th encodes a protein homologous to baculovirus inhibitors of apoptosis (IAPs), which we call Drosophila IAP1 (DIAP1). Overexpression of DIAP1 or a related protein, DIAP2, in the eye suppresses normally occurring cell death as well as death due to overexpression of rpr or head involution defective. IAP death-preventing activity localizes to the N-terminal baculovirus IAP repeats, a motif found in both viral and cellular proteins associated with death prevention.

Drosophila type II neuroblasts (NBs), like mammalian neural stem cells, deposit neurons through intermediate neural progenitors (INPs) that can each produce a series of neurons. Both type II NBs and INPs exhibit age-dependent expression of various transcription factors, potentially specifying an array of diverse neurons by combinatorial temporal patterning. Not knowing which mature neurons are made by specific INPs, however, conceals the actual variety of neuron types and limits further molecular studies. Here we mapped neurons derived from specific type II NB lineages and found that sibling INPs produced a morphologically similar but temporally regulated series of distinct neuron types. This suggests a common fate diversification program operating within each INP that is modulated by NB age to generate slightly different sets of diverse neurons based on the INP birth order. Analogous mechanisms might underlie the expansion of neuron diversity via INPs in mammalian brain.

Neuronal circuits are known to integrate nutritional information, but the identity of the circuit components is not completely understood. Amino acids are a class of nutrients that are vital for the growth and function of an organism. Here, we report a neuronal circuit that allows Drosophila larvae to overcome amino acid deprivation and pupariate. We find that nutrient stress is sensed by the class IV multidendritic cholinergic neurons. Through live calcium imaging experiments, we show that these cholinergic stimuli are conveyed to glutamatergic neurons in the ventral ganglion through mAChR. We further show that IP3R-dependent calcium transients in the glutamatergic neurons convey this signal to downstream medial neurosecretory cells (mNSCs). The circuit ultimately converges at the ring gland and regulates expression of ecdysteroid biosynthetic genes. Activity in this circuit is thus likely to be an adaptation that provides a layer of regulation to help surpass nutritional stress during development.

Early transplantation and grafting experiments suggest that body organs follow autonomous growth programs [1-3], therefore pointing to a need for coordination mechanisms to produce fit individuals with proper proportions. We recently identified Drosophila insulin-like peptide 8 (Dilp8) as a relaxin and insulin-like molecule secreted from growing tissues that plays a central role in coordinating growth between organs and coupling organ growth with animal maturation [4, 5]. Deciphering the function of Dilp8 in growth coordination relies on the identification of the receptor and tissues relaying Dilp8 signaling. We show here that the orphan receptor leucine-rich repeat-containing G protein-coupled receptor 3 (Lgr3), a member of the highly conserved family of relaxin family peptide receptors (RXFPs), mediates the checkpoint function of Dilp8 for entry into maturation. We functionally identify two Lgr3-positive neurons in each brain lobe that are required to induce a developmental delay upon overexpression of Dilp8. These neurons are located in the pars intercerebralis, an important neuroendocrine area in the brain, and make physical contacts with the PTTH neurons that ultimately control the production and release of the molting steroid ecdysone. Reducing Lgr3 levels in these neurons results in adult flies exhibiting increased fluctuating bilateral asymmetry, therefore recapitulating the phenotype of dilp8 mutants. Our work reveals a novel Dilp8/Lgr3 neuronal circuitry involved in a feedback mechanism that ensures coordination between organ growth and developmental transitions and prevents developmental variability.

Animal studies have been instrumental in providing knowledge about the molecular and neural mechanisms underlying drug addiction. Recently, the fruit fly Drosophila melanogaster has become a valuable system to model not only the acute stimulating and sedating effects of drugs but also their more complex rewarding properties. In this review, we describe the advantages of using the fly to study drug-related behavior, provide a brief overview of the behavioral assays used, and review the molecular mechanisms and neural circuits underlying drug-induced behavior in flies. Many of these mechanisms have been validated in mammals, suggesting that the fly is a useful model to understand the mechanisms underlying addiction.