果蝇非常规肌球蛋白的结构与功能

肌球蛋白是一类重要的分子马达,可以将ATP水解产生的能量转化成动能,沿由肌动蛋白组成的细丝运动。肌球蛋白构成一个大的基因家族,在许多细胞活动中起着重要作用,包括肌肉收缩、胞内转运、听觉、视觉等。果蝇基因组有13种肌球蛋白基因,包括2种常规肌球蛋白和11种非常规肌球蛋白。本文综述了近年来果蝇非常规肌球蛋白的研究进展。     

Neural circuitry: seeing the parts that make the picture

What are the neural correlates of vision? A recent study on Drosophila has described the incredible neuronal diversity in the fly visual system, and traced the circuits that underlie color vision.     

What makes transposable elements move in the Drosophila genome?

Transposable elements (TEs), by their capacity of moving and inducing mutations in the genome, are considered important drivers of species evolution. The successful invasions of TEs in genomes, despite their mutational properties, are an apparent paradox. TEs' transposition is usually strongly regulated to low value, but in some cases these elements can also show high transposition rates, which has been associated sometimes to changes in environmental conditions. It is evident that factors susceptible to induce transpositions in natural populations contribute to TE perpetuation. Different factors were proposed as causative agents of TE mobilization in a wide range of organisms: biotic and abiotic stresses, inter- and intraspecific crosses and populational factors. However, there is no clear evidence of the factors capable of inducing TE mobilization in Drosophila, and data on laboratory stocks show contradictory results. The aim of this review is to have an update critical revision about mechanisms promoting transposition of TEs in Drosophila, and to provide to the readers a global vision of the dynamics of these genomic elements in the Drosophila genome.     

Polarization vision: Drosophila enters the arena

Two new studies introduce the power of Drosophila genetics to polarization vision, revealing distinct photoreceptor inputs to polarotactic behaviour mediated by dorsal and ventral eye regions.     

The color-vision circuit in the medulla of Drosophila

BACKGROUND: Color vision requires comparison between photoreceptors that are sensitive to different wavelengths of light. In Drosophila, this is achieved by the inner photoreceptors (R7 and R8) that contain different rhodopsins. Two types of comparisons can occur in fly color vision: between the R7 (UV sensitive) and R8 (blue- or green sensitive) photoreceptor cells within one ommatidium (unit eye) or between different ommatidia that contain spectrally distinct inner photoreceptors. Photoreceptors project to the optic lobes: R1-R6, which are involved in motion detection, project to the lamina, whereas R7 and R8 reach deeper in the medulla. This paper analyzes the neural network underlying color vision into the medulla. RESULTS: We reconstruct the neural network in the medulla, focusing on neurons likely to be involved in processing color vision. We identify the full complement of neurons in the medulla, including second-order neurons that contact both R7 and R8 from a single ommatidium, or contact R7 and/or R8 from different ommatidia. We also examine third-order neurons and local neurons that likely modulate information from second-order neurons. Finally, we present highly specific tools that will allow us to functionally manipulate the network and test both activity and behavior. CONCLUSIONS: This precise characterization of the medulla circuitry will allow us to understand how color vision is processed in the optic lobe of Drosophila, providing a paradigm for more complex systems in vertebrates.     

Taste recognition: food for thought

The ability to identify food that is nutrient-rich and avoid toxic substances is essential for an animal's survival. Although olfaction and vision contribute to food detection, the gustatory system acts as a final checkpoint control for food acceptance or rejection behavior. Recent studies with model organisms such as mice and Drosophila have identified candidate taste receptors and examined the logic of taste coding in the periphery. Despite differences in terms of gustatory anatomy and taste-receptor families, these gustatory systems share a basic organization that is different from other sensory systems. This review will summarize our current understanding of taste recognition in mammals and Drosophila, highlighting similarities and raising several as yet unanswered questions.     

Natural variation of ebony gene controlling thoracic pigmentation in Drosophila melanogaster

We identified the causal genetic variation for the difference in the thoracic trident pigmentation intensity between two wild-derived strains of Drosophila melanogaster. It was found to be the difference in expression level of ebony, which codes for an enzyme in the melanin-synthesis pathway and has pleiotropic effects on vision and behavior.     

Filling the gap in vitamin A research. Molecular identification of an enzyme cleaving beta-carotene to retinal

Vitamin A and its derivatives (retinoids) are essential components in vision; they contribute to pattern formation during development and exert multiple effects on cell differentiation with important clinical implications. It has been known for 50 years that the key step in the formation of vitamin A is the oxidative cleavage of beta-carotene; however, this enzymatic step has resisted molecular analysis. A novel approach enabled us to clone and identify a beta-carotene dioxygenase from Drosophila melanogaster, expressing it into the background of a beta-carotene (provitamin A)-synthesizing and -accumulating Escherichia coli strain. The carotene-cleaving enzyme, identified here for the first time on the molecular level, is the basis of the numerous branches of vitamin A action and links plant and animal carotene metabolism.     

Master regulatory genes; telling them what to do

In 1995, the eyeless (ey) gene was dubbed the "master-regulator" of eye development in Drosophila. Not only is ey required for eye development, but its misexpression can convert many other tissues into eye, including legs, wings and antennae.(1) ey is remarkable for its ability to drive coordinate differentiation of the multiple cell types that have to differentiate in a very precise pattern to construct the fly eye, and for its power to override the previous differentiation programs of many other diverse tissues. Even more remarkable, the ey homolog Pax6 and homologs of other eye determination genes from Drosophila are also required for eye development in vertebrates,(2,3) prompting reassessment of the evolution of vision throughout the animal kingdom.(4,5) Now Kumar and Moses have published a study that throws a new light on ey function in Drosophila.(6) According to their work, ey becomes a master regulator of eye development much later than previously thought, and is regulated by signalling through the Notch and EGFR signaling pathways.     

Drosophila Pax-6/eyeless is essential for normal adult brain structure and function

A role for the Pax-6 homologue eyeless in adult Drosophila brain development and function is described. eyeless expression is detected in neurons, but not glial cells, of the mushroom bodies, the medullar cortex, the lateral horn, and the pars intercerebralis. Furthermore, severe defects in adult brain structures essential for vision, olfaction, and for the coordination of locomotion are provoked by two newly isolated mutations of Pax-6/eyeless that result in truncated proteins. Consistent with the morphological lesions, we observe defective walking behavior for these eyeless mutants. The implications of these data for understanding postembryonic brain development and function in Drosophila are discussed.     

Blockade of neurotransmission in Drosophila mushroom bodies impairs odor attraction, but not repulsion

Olfaction can elicit a rich perceptual experience. It is not known, however, whether olfactory information is decomposed into various components and processed in distinct perceptual centers as in other sensory systems, such as vision, where neural representations of different visual sensations are segregated in different cortical regions, despite the fact that multiple structures of the primary olfactory cortex receive projections from the olfactory bulb. Here, we use Drosophila as a model to investigate whether different olfactory information may be processed in separate brain structures. Organizations of the peripheral olfactory system are remarkably similar from mammals to insects. As in vertebrates, the olfactory pathway in Drosophila follows similar convergence and divergence, and multiple high-order structures in the Drosophila brain, including the mushroom body (MB) and lateral horn (LH) of the protocerebrum, receive olfactory input. We specifically blocked neurotransmission in the MB while leaving the LH unaffected and examined its effect on olfactory avoidance and attraction behaviors. We show that blocking MB activity disrupted responses to attractive, but not repulsive, odors, and this finding suggests that attractive and repulsive olfactory information may be separately processed in higher olfactory centers of the Drosophila brain.     

Nucleotide variation at the no-on-transient A gene in Drosophila littoralis

The no-on-transient A (nonA) gene encodes a putative RNA-binding protein, and mutations in this gene are known to affect vision, male courtship song and viability in Drosophila melanogaster. Here we have sequenced the coding region of the nonA gene of Drosophila littoralis and compared it with those of Drosophila virilis and D. melanogaster. All portions of nonA appeared to be conserved between D. littoralis and D. virilis, while the 5' region of the gene of these two species showed high divergence from that of a more distantly-related species, D. melanogaster. The same was true for the glycine repeat regions. No significant deviation from neutrality was observed in the analysis of intraspecific nucleotide variation in 5' or 3' region of the nonA gene in D. littoralis population. Also, comparison of D. littoralis sequences with homologous sequence of D. virilis suggests that the gene is evolving neutrally in D. virilis group. Divergence of the 5' regions between D. virilis group species and D. melanogaster could be a result of positive selection, but this finding is obscured by the long divergence time of the species groups.     

Towards a better understanding of carotenoid metabolism in animals

Vitamin A derivatives (retinoids) are essential components in vision; they contribute to pattern formation during development and exert multiple effects on cell differentiation with important clinical implications. All naturally occurring vitamin A derives by enzymatic oxidative cleavage from carotenoids with pro-vitamin A activity. To become biologically active, these plant-derived compounds must first be absorbed, then delivered to the site of action in the body, and metabolically converted to the real vitamin. Recently, molecular players of this pathway were identified by the analysis of blind Drosophila mutants. Similar genome sequences were found in vertebrates. Subsequently, these homologous genes were cloned and their gene products were functionally characterized. This review will summarize the advanced state of knowledge about the vitamin A biosynthetic pathway and will discuss biochemical, physiological, developmental and medical aspects of carotenoids and their numerous derivatives.     

The agrin/perlecan-related protein eyes shut is essential for epithelial lumen formation in the Drosophila retina

The formation of epithelial lumina is a fundamental process in animal development. Each ommatidium of the Drosophila retina forms an epithelial lumen, the interrhabdomeral space, which has a critical function in vision as it optically isolates individual photoreceptor cells. Ommatidia containing an interrhabdomeral space have evolved from ancestral insect eyes that lack this lumen, as seen, for example, in bees. In a genetic screen, we identified eyes shut (eys) as a gene that is essential for the formation of matrix-filled interrhabdomeral space. Eys is closely related to the proteoglycans agrin and perlecan and secreted by photoreceptor cells into the interrhabdomeral space. The honeybee ortholog of eys is not expressed in photoreceptors, raising the possibility that recruitment of eys expression has made an important contribution to insect eye evolution. Our findings show that the secretion of a proteoglycan into the apical matrix is critical for the formation of epithelial lumina in the fly retina.     

A putative Drosophila pheromone receptor expressed in male-specific taste neurons is required for efficient courtship

Propagation in higher animals requires the efficient and accurate display of innate mating behaviors. In Drosophila melanogaster, male courtship consists of a stereotypic sequence of behaviors involving multiple sensory modalities, such as vision, audition, and chemosensation. For example, taste bristles located in the male forelegs and the labial palps are thought to recognize nonvolatile pheromones secreted by the female. Here, we report the identification of the putative pheromone receptor GR68a, which is expressed in chemosensory neurons of about 20 male-specific gustatory bristles in the forelegs. Gr68a expression is dependent on the sex determination gene doublesex, which controls many aspects of sexual differentiation and is necessary for normal courtship behavior. Tetanus toxin-mediated inactivation of Gr68a-expressing neurons or transgene-mediated RNA interference of Gr68a RNA leads to a significant reduction in male courtship performance, suggesting that GR68a protein is an essential component of pheromone-driven courtship behavior in Drosophila.     

Motion processing streams in Drosophila are behaviorally specialized

Motion vision is an ancient faculty, critical to many animals in a range of ethological contexts, the underlying algorithms of which provide central insights into neural computation. However, how motion cues guide behavior is poorly understood, as the neural circuits that implement these computations are largely unknown in any organism. We develop a systematic, forward genetic approach using high-throughput, quantitative behavioral analyses to identify the neural substrates of motion vision in Drosophila in an unbiased fashion. We then delimit the behavioral contributions of both known and novel circuit elements. Contrary to expectation from previous studies, we find that orienting responses to motion are shaped by at least two neural pathways. These pathways are sensitive to different visual features, diverge immediately postsynaptic to photoreceptors, and are coupled to distinct behavioral outputs. Thus, behavioral responses to complex stimuli can rely on surprising neural specialization from even the earliest sensory processing stages.     

Testing Drosophila Olfaction with a Y-maze Assay

Detecting signals from the environment is essential for animals to ensure their survival. To this aim, they use environmental cues such as vision, mechanoreception, hearing, and chemoperception through taste, via direct contact or through olfaction, which represents the response to a volatile molecule acting at longer range. Volatile chemical molecules are very important signals for most animals in the detection of danger, a source of food, or to communicate between individuals. Drosophila melanogaster is one of the most common biological models for scientists to explore the cellular and molecular basis of olfaction. In order to highlight olfactory abilities of this small insect, we describe a modified choice protocol based on the Y-maze test classically used with mice. Data obtained with Y-mazes give valuable information to better understand how animals deal with their perpetually changing environment. We introduce a step-by-step protocol to study the impact of odorants on fly exploratory response using this Y-maze assay.     

果蝇基因组与功能基因研究进展

黑腹果蝇Drosophila melanogaster是生物科学研究中重要的模式动物之一。2000年,黑腹果蝇全基因组测序完成,随后基因组序列质量不断完善,对其功能基因进行深入研究,为其他高等动物基因组和功能基因的研究提供了巨大帮助。本文综述了近年来基因组功能元件、比较基因组学等方面的最新研究成果,着重介绍了功能基因在Hh信号通路、细胞凋亡方面的研究进展,并对最新的功能基因研究技术进行了简要概述。     

Fondue and transglutaminase in the Drosophila larval clot

Hemolymph coagulation is vital for larval hemostasis and important in immunity, yet the molecular basis of coagulation is not well understood in insects. Of the larval clotting factors identified in Drosophila, Fondue is not conserved in other insects, but is notable for its effects on the clot's physical properties, a possible function in the cuticle, and for being a substrate of transglutaminase. Transglutaminase is the only mammalian clotting factor found in Drosophila, and as it acts in coagulation in other invertebrates, it is also likely to be important in clotting in Drosophila. Here we describe a Fondue-GFP fusion construct that labels the cuticle and clot, and show that chemical inhibition and RNAi knockdown of the Drosophila transglutaminase gene affect clot properties and composition in ways similar to knockdown of the fon gene. Thus, Fondue appears to be incorporated into the cuticle and is a key transglutaminase substrate in the clot. This is also the first direct functional confirmation that transglutaminase acts in coagulation in Drosophila.     

Quantitative mechanical evaluation and analysis of Drosophila embryos through the stages of embryogenesis

The fruit fly Drosophila embryo is one of the most important model organisms in genetics and developmental biology research. To better understand the biomechanical properties involved in Drosophila embryo research, this work presents a mechanical characterization of living Drosophila embryos through the stages of embryogenesis. Measurements of the mechanical forces of Drosophila embryos are implemented using a novel, in situ, and minimally invasive force sensing tool with a resolution in the range of microN. The measurements offer an essential understanding of penetration force profiles during the microinjection of Drosophila embryos. Sequentially quantitative evaluation and analysis of the mechanical properties, such as Young's modulus, stiffness, and mechanical impedance of living Drosophila embryos are performed by extracting the force measurements throughout the stages of embryogenesis. Experimental results illustrate the changing mechanical properties of Drosophila embryos during development, and thus mathematical models are proposed. The evaluation provides a critical step toward better understanding of the biomechanical properties of Drosophila embryos during embryogenesis, and could contribute to more efficient and significant genetic and embryonic development research on Drosophila.