Notch signaling plays an essential role in the processes of embryogenesis and cellular differentiation, and it is believed that the oncogenic effects of dysregulated Notch signaling are an anomalous reflection of the normal functions of this cascade. Nonetheless, the cellular events associated with oncogenic Notch signaling have thus far remained elusive. In a recent report, Ferres‐Marco et al.1 described how they used the Drosphila eye as a model system and found that elevated Notch signaling in combination with activation of components (...) of the Polycomb complex of transcriptional repressors led to metastatic growth of tumors through epigenetic silencing of the Rbf gene. Rbf is the Drosophila homologue of the retinoblastoma tumor‐suppressor gene (Rb), thus it represents a novel link between Notch signaling, tumor growth and metastasis. BioEssays 28: 692–695, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Drosophila imaginal discs (appendage primordia) have proved invaluable for deciphering cellular and molecular mechanisms of animal development. By combining the accessibility of the discs with the genetic tractability of the fruit fly, researchers have discovered key mechanisms of growth control, pattern formation and long‐range signaling. One of the principal experimental attractions of discs is their anatomical simplicity — they have long been considered to be cellular monolayers. During larval stages, however, the growing discs are 2‐sided sacs composed of a (...) columnar epithelium on one side and a squamous ‘peripodial’ epithelium on the other. Recent studies suggest important roles for peripodial epithelia in processes previously assumed to be confined to columnar cell monolayers. BioEssays 23:691–697, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Determination of cell fate in the developing eye of Drosophila depends on a precise sequence of cellular interactions which generate the stereotypic array of ommatidia. In the eye imaginal disc, an initially unpatterned epithelial sheath of cells, the first step in this process may be the specification of R8 photoreceptor cells at regular intervals. Genes such as Notch and scabrous, known to be involved in bristle development, alos participate in this process, suggesting that the specification of ommatidial founder cells (...) and the formation of sensory organs in the adult epidermis may involve a similar mechanism, that of lateral inhibition. The subsequent steps of ommatidial assembly, following R8 assignment, involve a different mechanism: Undetermined cells read their position based on the contacts they make with neighbors that have already begun to differentiate. The development of the R7 photoreceptor cell, one of the eight photoreceptor cells in the ommatidium, is best understood. An important role seems to be played by sevenless, a receptor tyrosine kinase on the surface of the R7 precursor. It transmits the positional information– most likely encoded by the boss protein on the neighboring R8 cell membrane – into the cell via its tyrosine kinase, which activates a signal transduction cascade. Constitutive activation of the sevenless kinase by overexpression of an N‐terminally truncated form results in the diversion of other ommatidial cells into the R7 pathway suggesting that activation of the sevenless signalling pathway is sufficient to specify R7 development. Genetic dissection of this pathway should therefore identify components of a signalling cascade activated by a tyrosine kinase. (shrink)

Stalk‐eyed flies of the family Diopsidae exhibit a unique form of hypercephaly, which has evolved under both natural and sexual selection. Male hypercephaly is used by female diopsids as an indicator of male quality. By choosing to mate with males expressing the most‐exaggerated hypercephaly, females can benefit both from the enhanced fertility of these males and the transmission of other heritable advantages to their offspring. Stalk‐eyed flies are close relatives of the model organism, Drosophila melanogaster. We have shown that (...) similar genetic and cellular mechanisms regulate the initial development of the head capsule in fruitflies and diopsids. The great diversity of stalk‐eyed fly species, exhibiting varying degrees of hypercephaly and sexual dimorphism, constitutes a major advantage for comparative studies of their development and evolution. BioEssays 29: 300–307, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

The compound eyes of insects exhibit stunning variation in size, structure, and function, which has allowed these animals to use their vision to adapt to a huge range of different environments and lifestyles, and evolve complex behaviors. Much of our knowledge of eye development has been learned from Drosophila, while visual adaptations and behaviors are often more striking and better understood from studies of other insects. However, recent studies in Drosophila and other insects, including bees, beetles, and butterflies, (...) have begun to address this gap by revealing the genetic and developmental bases of differences in eye morphology and key new aspects of compound eye structure and function. Furthermore, technical advances have facilitated the generation of high‐resolution connectomic data from different insect species that enhances our understanding of visual information processing, and the impact of changes in these processes on the evolution of vision and behavior. Here, we review these recent breakthroughs and propose that future integrated research from the development to function of visual systems within and among insect species represents a great opportunity to understand the remarkable diversification of insect eyes and vision. (shrink)

The Drosophila compound eye is an excellent experimental system for analysing fate induction of identifiable single cells. Each ommatidium, a unit eye, contains eight photoreceptors (R1‐R8), and the differentiation of these photoreceptors occurs in the larval eye imaginal disc in discrete steps: first R8 is determined, then R2/R5, R3/R4, R1/R6 and finally R7. Induction of R7, in particular, has been extensively studied at the molecular level. The R8 photoreceptor presents on its surface a ligand, Bride of Sevenless, that binds (...) and activates Sevenless receptor tyrosine kinase in the R7 precursor. Autophosphorylated Sevenless initiates a Ras1‐mediated cascade, which eventually activates transcription factors in the nucleus via Raf1 and MAP kinases, resulting in R7 development. However, recent studies indicate that Sevenless (Sev) functions just to neuralize the cell and has no role in R7 fate determination per se. It appears that the R7 fate may represent the lowest rung of a ‘neuronal ground state’, which is attained without any specific inductive cue. It is plausible that the R7 precursor is actively prevented from taking on the neuronal fate and this inhibition is removed by activation of Sev. (shrink)

Perception is a first-person internal sensation induced within the nervous system at the time of arrival of sensory stimuli from objects in the environment. Lack of access to the first-person properties has limited viewing perception as an emergent property and it is currently being studied using third-person observed findings from various levels. One feasible approach to understand its mechanism is to build a hypothesis for the specific conditions and required circuit features of the nodal points where the mechanistic operation of (...) perception take place for one type of sensation in one species and to verify it for the presence of comparable circuit properties for perceiving a different sensation in a different species. The present work explains visual perception in mammalian nervous system from a first-person frame of reference and provides explanations for the homogeneity of perception of visual stimuli above flicker fusion frequency, the perception of objects at locations different from their actual position, the smooth pursuit and saccadic eye movements, the perception of object borders, and perception of pressure phosphenes. Using results from temporal resolution studies and the known details of visual cortical circuitry, explanations are provided for (a) the perception of rapidly changing visual stimuli, (b) how the perception of objects occurs in the correct orientation even though, according to the third-person view, activity from the visual stimulus reaches the cortices in an inverted manner and (c) the functional significance of well-conserved columnar organization of the visual cortex. A comparable circuitry detected in a different nervous system in a remote species-the olfactory circuitry of the fruit fly Drosophila melanogaster-provides an opportunity to explore circuit functions using genetic manipulations, which, along with high-resolution microscopic techniques and lipid membrane interaction studies, will be able to verify the structure-function details of the presented mechanism of perception. (shrink)

The Drosophila Bolwig organs are small photoreceptor bundles that facilitate the phototactic behavior of the larva. Comparative literature suggests that these highly reduced visual organs share evolutionary ancestry with the adult compound eye. A recent molecular genetic study produced the first detailed account of the mechanisms controlling differential opsin expression and photoreceptor subtype determination in these enigmatic eyes of the Drosophila larva. Here, the evolutionary implications are examined, taking into account the dynamic diversification of opsin genes and the (...) spatial regulation of opsin homolog expression in other insects. It is concluded that, consistent with their common evolutionary roots, the Drosophila larval and adult eyes use the same mechanisms for the regulation of opsin expression and photoreceptor cell fate specification. Strikingly, the structurally highly derived Bolwig organs retained a more ancestral state of opsin expression and regulation. Inconspicuous in size, the Drosophila larval eyes deliver useful lessons in the reconstruction of homology between neuronal cell types with gene expression data, and on the conservative nature of gene regulatory network evolution during the emergence of novel organs from ancestral templates. BioEssays 30:980–993, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

This review is focused on recent advances in our understanding of the development of coordinated cell polarity, through experiments on the Drosophila compound eye. Each eye facet (or “ommatidium”) contains a set of eight photoreceptor cells, placed so that their rhabdomeres form an asymmetric trapezoid. The array of ommatidia is organized so that these trapezoids are aligned in two mirror-image fields, dorsal and ventral to the eye midline (or “equator”). The development of this pattern depends on two systems of (...) positional information that inform the cluster of cells that will form an ommatidium of anterior/posterior (a/p) and dorsal/ventral (d/v) direction. The former (a/p) is encoded by a progressive wave of development (the morphogenetic furrow). The latter (d/v) involves molecules known to act in tissue polarity in other organs and organisms. Our understanding of the function of these molecules rests not only on their mutant phenotypes, biochemistry, and expression patterns, but also on the spatial effects when mutant patches of cells are made (genetic mosaics). BioEssays 21:275–285, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

Over 10 years ago, Pax‐6 was shown to play an evolutionarily conserved role in controlling eye formation from Drosophila to humans.1 Since then, the identification of an entire cascade of conserved eye determination genes has brought a new understanding to the developmental relationship between the insect compound eye and the vertebrate camera eye.2 Additional studies are now beginning to suggest that even late aspects of eye development, including cell type specification, also share common molecular machinery. In this commentary, I (...) will discuss some of these findings, with a particular focus on the recent study by Dyer et al.3 describing a novel role for the Prox1 transcription factor in specifying horizontal cells in the mouse retina. As Prospero, the Drosophila homolog of Prox1, also participates in retinal cell specification, these data provide a forum for asking new questions concerning pathways that may regulate retinogenesis across evolution. BioEssays 25:921–925, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

The open rhabdoms of the fly's eye enhance absolute sensitivity but to avoid compromising spatial acuity they require precise optical geometry and neural connections.1 This neural superposition system evolved from the ancestral insect eye, which has fused rhabdoms. A recent paper by Zelhof and co‐workers2 shows that the Drosophila gene spacemaker (spam) is necessary for development of open rhabdoms, and suggests that mutants revert to an ancestral state. Here I outline how open rhabdoms and neural superposition may have evolved (...) via nocturnal intermediates, and discuss the implications for the role of spam in insect phylogeny. BioEssays 29: 111–115, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Pax genes are a family of development control genes that encode nuclear transcription factors. They are characterized by the presence of the paired domain, a conserved amino acid motif with DNA‐binding activity. Originally, paired‐box‐containing genes were detected in Drosophila malenogaster, where they exert multiple functions during embryogenesis. In vertebrates, Pax genes are also involved in embryogenesis. Mutations in four out of nine characterized Pax genes have been associated with either congenital human diseases such as Waardenburg syndrome (PAX3), Aniridia (PAX6), (...) Peter's anomaly (PAX6), renal coloboma syndrome (PAX2), Small eye (Pax6), (Pax21Neu), which all show defects in development. Recently, analysis of spontaneous and transgenic mouse mutants has revealed that vertebrate Pax genes are key regulators during organogenesis of kidney, eye, ear, nose, limb muscles, vertebral column and brain. Like their Drosophila counterparts, vertebrate Pax genes are involved in pattern formation during embryogenesis, possibly by determiing the time and place of organ initiation of morphogenesis. For most tissues, however, the nature of the primary development action of Pax transcription factors remains to be elucidated. One predominant theme is signal transduction during tissue interactions, which may lead to a position‐specific regulation of cell proliferation. (shrink)

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. BioEssays 23:763–766, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

First isolated in the fly and now characterised in vertebrates, the Slit proteins have emerged as pivotal components controlling the guidance of axonal growth cones and the directional migration of neuronal precursors. As well as extensive expression during development of the central nervous system (CNS), the Slit proteins exhibit a striking array of expression sites in non-neuronal tissues, including the urogenital system, limb primordia and developing eye. Zebrafish Slit has been shown to mediate mesodermal migration during gastrulation, while Drosophila (...) slit guides the migration of mesodermal cells during myogenesis. This suggests that the actions of these secreted molecules are not simply confined to the sphere of CNS development, but rather act in a more general fashion during development and throughout the lifetime of an organism. This review focuses on the non-neuronal activities of Slit proteins, highlighting a common role for the Slit family in cellular migration. (shrink)

Sensory organs are specialized to receive different kinds of input from the outside world. However, common features of their development suggest that they could have a shared evolutionary origin. In a recent paper, Niwa et al.1 show that three Drosophila adult sensory organs all rely on the spatial signals Decapentaplegic and Wingless to specify their position, and the temporal signal ecdysone to initiate their development. The proneural gene atonal is an important site for integration of these regulatory inputs. These (...) results suggest the existence of a primitive sensory organ precursor, which would differentiate according to the identity of its segment of origin. The authors argue that the eyeless gene controls eye disc identity, indirectly producing an eye from the sensory organ precursor within this disc. BioEssays 26:825–828, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The members of the Six gene family were identified as homologues of Drosophila sine oculis which is essential for compound-eye formation. The Six proteins are characterized by the Six domain and the Six-type homeodomain, both of which are essential for specific DNA binding and for cooperative interactions with Eya proteins. Mammals possess six Six genes which can be subdivided into three subclasses, and mutations of Six genes have been identified in human genetic disorders. Characterization of Six genes from various (...) animal phyla revealed the antiquity of this gene family and roles of its members in several different developmental contexts. Some members retain conserved roles as components of the Pax-Six-Eya-Dach regulatory network, which may have been established in the common ancestor of all bilaterians as a toolbox controlling cell proliferation and cell movement during embryogenesis. Gene duplications and cis-regulatory changes may have provided a basis for diverse functions of Six genes in different animal lineages. (shrink)

Insect vision is nothing if not active. The regular head movements, called saccades, enable the fly Drosophila to keep a straight path in flight despite inequalities in the thrust of the wings. Using their own motion, bees in flight measure the ranges of nearby objects. A long history of research shows that bees discriminate visually in ways that depend on their activity or task, so we must distinguish between vision during flying, fixating or hovering and landing.Bees return again and (...) again for a reward of sugar solution and use their eyes to find their way. In an apparatus that makes them discriminate between two simulataneously visible but regularly interchanged targets, seen at a distance of 27 cm, bees are able to distinguish a remarkable number of simple patterns, but they fail in certain critical cases. The results can be explained with the hypothesis that bees have several broadly tuned overlapping filters with large fields that respond to the predominant orientation in a region of the image, and others for radial and circular patterns. Together with colour, these filters are independent of range. Bees prefer to use landmarks where they can, then global pattern at the largest scale, and lastly the detail around the goal. The way that discrimination of one visual feature is independent of other variables can be explained by models analogous to the colour triangle in colour discrimination. (shrink)

The Hawaiian Drosophila have been a model system for evolutionary, ecological, and ethological studies since the inception of the Hawaiian Drosophila Project in the 1960s. Here we review the past and present research on this incredible lineage and provide a prospectus for future directions on genomics and microbial interactions. While the number of publications on this group has waxed and waned over the years, we assert that recent systematic, biogeographic, and ecological studies have reinvigorated Hawaiian Drosophila as (...) an evolutionary model system. The characteristics that distinguish good model clades from good model organisms (e.g., Drosophila melanogaster) are somewhat different so we first define what constitutes a good evolutionary model. We argue that the Hawaiian Drosophila possess many desired aspects of a good evolutionary model, describe how this group of geographically isolated flies have been used in the past, and propose some exciting avenues for future evolutionary research on this diverse, dynamic clade of Drosophila. (shrink)

Secreted signaling molecules act as morphogens to control patterning and growth in many developing tissues. Since locally produced morphogens spread to form a concentration gradient in the surrounding tissue, spreading is generally thought to be the key step in the non‐autonomous actions. Here, we review recent advances in tool development to investigate morphogen function using the role of decapentaplegic (Dpp)/bone morphogenetic protein (BMP)‐type ligand in the Drosophila wing disc as an example. By applying protein binder tools to distinguish between (...) the roles of Dpp spreading and local Dpp signaling, we found that Dpp signaling in the source cells is important for wing patterning and growth but Dpp spreading from this source cells is not as strictly required as previously thought. Given recent studies showing unexpected requirements of long‐range action of different morphogens, manipulating endogenous morphogen gradients by synthetic protein binder tools could shed more light on how morphogens act in developing tissues. (shrink)

Completing the translation of Derrida’s monumental work Right to Philosophy (the first part of which has already appeared under the title of Who’s Afraid of Philosophy?), Eyes of the University brings together many of the philosopher’s most important texts on the university and, more broadly, on the languages and institutions of philosophy. In addition to considerations of the implications for literature and philosophy of French becoming a state language, of Descartes’ writing of the Discourse on Method in French, and of (...) Kant’s and Schelling’s philosophies of the university, the volume reflects on the current state of research and teaching in philosophy and on the question of what Derrida calls a “university responsibility.” Examining the political and institutional conditions of philosophy, the essays collected here question the growing tendency to orient research and teaching towards a programmable and profitable end. The volume is therefore invaluable for the light it throws upon an underappreciated aspect of Derrida’s own engagement, both philosophical and political, in struggles against the stifling of philosophical research and teaching. As a founding member of the Research Group on the Teaching of Philosophy and as one of the conveners of the Estates General of Philosophy, Derrida was at the forefront of the struggle to preserve and extend the teaching of philosophy as a distinct discipline, in secondary education and beyond, in the face of conservative government education reforms in France. As one of the founders of the Collège International de Philosophie, he worked to provide a space for research in and around philosophy that was not accepted or legitimated in other institutions. Documenting and reflecting upon these engagements, Eyes of the University brings together some of the most important and incisive of Derrida’s works. (shrink)

Drosophila telomeres comprise DNA sequences that differ dramatically from those of other eukaryotes. Telomere functions, however, are similar to those found in telomerase‐based telomeres, even though the underlying mechanisms may differ. Drosophila telomeres use arrays of retrotransposons to maintain chromosome length, while nearly all other eukaryotes rely on telomerase‐generated short repeats. Regardless of the DNA sequence, several end‐binding proteins are evolutionarily conserved. Away from the end, the Drosophila telomeric and subtelomeric DNA sequences are complexed with unique combinations (...) of proteins that also modulate chromatin structure elsewhere in the genome. Maintaining and regulating the transcriptional activity of the telomeric retrotransposons in Drosophila requires specific chromatin structures and, while telomeric silencing spreads from the terminal repeats in yeast, the source of telomeric silencing in Drosophila is the subterminal arrays. However, the subterminal arrays in both species may be involved in telomere–telomere associations and/or communication. BioEssays 30:25–37, 2008. © 2007 Wiley Periodicals, Inc. (shrink)

The link between oncogenesis and normal development is well illustrated by the study of the Wnt family of proteins. The first Wnt gene (int‐1) was identified over a decade ago as a proto‐oncogene, activated in response to proviral insertion of a mouse mammary tumor virus. Subsequently, the discovery that Drosophila wingless, a developmentally important gene, is homologous to int‐1 supported the notion that int‐1 may have a role in normal development. In the last few years it has been recognized (...) that int‐1 and Wingless belong to a large family of related glyco‐proteins found in vertebrates and invertebrates. In recognition of this, members of this family have been renamed Wnts, an amalgam of int and Wingless. Investigation of Wnt genes in Xenopus and mouse indicates that Wnts have a role in cell proliferation, differentiation and body axis formation. Further analysis in Drosophila has revealed that Wingless function is required in several developmental processes in the embryo and imaginal discs. In addition, a genetic approach has identified some of the molecules required for the transmission and reception of the Wingless signal. We will review recent data which have contributed to our growing understanding of the function and mechanism of Drosophila Wingless signaling in cell fate determination, growth and specification of pattern. (shrink)

Hox complex genes are key developmental regulators highly conserved throughout evolution. The encoded proteins share a 60‐amino‐acid DNA‐binding motif, the homeodomain, and function as transcription factors to control axial patterning. An important question concerns the nature and function of genes acting downstream of Hox proteins. This review focuses on Drosophila, as little is known about this question in other organisms. The noticeable progress gained in the field during the past few years has significantly improved our current understanding of how (...) Hox genes control diversified morphogenesis. Here we summarise the strategies deployed to identify Hox target genes and discuss how their function contributes to pattern formation and morphogenesis. The regulation of target genes is also considered with special emphasis on the mechanisms underlying the specificity of action of Hox proteins in the whole animal. (shrink)

The complete sequencing of the genome of the fruit fly Drosophila melanogaster offers the prospect of detailed functional analysis of the extensive gene families in this genetic model organism. Comprehensive functional analysis of family members is facilitated by access to a robust, stable and inducible expression system in a fly cell line. Here we show how the Schneider S2 cell line, derived from the Drosophila embryo, provides such an expression system, with the bonus that radioligand binding studies, second (...) messenger assays, ion imaging, patch‐clamp electrophysiology and gene silencing can readily be applied. Drosophila is also ideal for the study of new control strategies for insect pests since the receptors and ion channels that many new animal health drugs and crop protection chemicals target can be expressed in this cell line. In addition, many useful orthologues of human disease genes are emerging from the Drosophila genome and the study of their functions and interactions is another area for postgenome applications of S2 cell lines. BioEssays 24:1066–1073, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

The Drosophila position‐specific antigens are a family of cell‐surface glycoprotein complexes showing spatially restricted patterns of expression. Changes in these distributions correlate with morphogenetic events like compartment‐alization and the formation of grooves and folds during tissue organization. The complexes each contain a common component associated with different variable components. Different tissues, organs and regions of the body express complexes containing different subsets of variable components. The structure of the complexes resembles that of the family of vertebrate receptors for fibronectin, (...) molecules which function in morphogenetic processes involving cell migration and attachment. It is possible that the position‐specific antigens have a similar role in fly development. (shrink)

Drosophila males sing a courtship song to achieve copulations with females. Females were recently found to sing a distinct song during copulation, which depends on male seminal fluid transfer and delays female remating. Here, it is hypothesized that female copulation song is a signal directed at the copulating male and changes ejaculate allocation. This may alter female remating and sperm usage, and thereby affect postcopulatory mate choice. Mechanisms of how female copulation song is elicited, how males respond to copulation (...) song, and how remating is modulated, are considered. The potential adaptive value of female signaling during copulation is discussed with reference to vertebrate copulation calls and their proposed function in eliciting mate guarding. Female copulation song may be widespread within the Drosophila genus. This newly discovered behavior opens many interesting avenues for future research, including investigation of how sexually dimorphic neuronal circuits mediate communication between nervous system and reproductive organs. (shrink)

In this book Wilber presents a model of consciousness that encompasses empirical, psychological, and spiritual modes of understanding. Wilber examines three realms of knowledge: the empirical realm of the senses, the rational realm of the mind, and the contemplative realm of the spirit. Eye to Eye points the way to a broader, more inclusive understanding of ourselves and the universe.

From stem cells to oocyte, Drosophila germ cells undergo a short, defined lineage. Molecular genetic analyses of a collection of female sterile mutations have indicated that a germ cell‐specific organelle called the fusome has a central role at several steps in this lineage. The fusome grows from a prominent spherical organelle to an elongated and branched structure that connects all mitotic sisters in a germ cell syncytium. The organelle is assembled from proteins normally found in the membrane skeleton and, (...) additionally, contains an extensive membranous reticulum, the probable product of differentiation‐dependent vesicle trafficking. This review briefly summarizes a current view of the processes that drive germ cell differentiation, particularly the various roles that the fusome might play in regulating the developmental events. Future efforts will consider to what extent an organelle assembly‐dependent model for differentiation is heuristic and whether the Drosophila fusome represents a homolog of a similar organelle in vertebrate lymphocytes. (shrink)

The chorion genes of Drosophila are amplified in response to developmental signals in the follicle cells of the ovary prior to their transcription. Their expression is regulated both temporally and spatially within this tissue. They thus serve as models both for the regulation of DNA replication and of developmental transcription. The regulatory elements for DNA amplification have been delineated. Their analysis reveals that amplification is mediated by several regulatory regions and initiates at defined origins within the chorion cluster. Proteins (...) involved in amplification are being identified both by mutations affecting amplification and by DNA binding studies. Regulatory elements for temporal as well as spatial control of chorion gene, expression have been characterized, and two candidate transcription factor genes have been cloned. (shrink)

The three cycles of cell division immediately following theformation of the cellular blastoderm during Drosophila embryogenesis display an invariant pattern(1,2). Bursts of transcription of a gene called string are required and sufficient to trigger mitosis at this time during development(3). The activator of mitosis encoded by the string gene is a positive regulator of cdc2 kinase and a Drosophila homologue of the Saccharomyces pombe cdc25 tyrosine phosphatase(4,5). Evidence presented in a recent paper(6) demonstrates that transcription of string, and (...) hence the timing and pattern of mitosis in the postblastoderm embryo, is under complex developmental control. Several lines of evidence support this interpretation, including the analysis of string transcription in pattern formation mutants, cell cycle arrest mutants, and the preliminary characterization of an extensive cis‐acting regulatory region. (shrink)

The view that complexity increases in evolution is uncontroversial, yet little is known about the possible causes of such a trend. One hypothesis, the Zero Force Evolutionary Law (ZFEL), predicts a strong drive toward complexity, although such a tendency can be overwhelmed by selection and constraints. In the absence of strong opposition, heritable variation accumulates and complexity increases. In order to investigate this claim, we evaluate the gross morphological complexity of laboratory mutants in Drosophila melanogaster, which represent organisms that (...) arise in a context where selective forces are greatly reduced. Complexity was measured with respect to part types, shape, and color over two independent focal levels. Compared to the wild type, we find that D. melanogaster mutants are significantly more complex. When the parts of mutants are categorized by degree of constraint, we find that weakly constrained parts are significantly more complex than more constrained parts. These results support the ZFEL hypothesis. They also represent a first step in establishing the domain of application of the ZFEL and show one way in which a larger empirical investigation of the principle might proceed. (shrink)

Tumor suppressor genes represent a broad class of genes that normally function in the negative regulation of cell proliferation. Loss‐of‐function mutations in these genes lead to unrestrained cell proliferation and tumor formation. A fundamental understanding of how tumor suppressor genes regulate cell proliferation and differentiation should reveal important aspects of signalling pathways and cell cycle control. A recent report describing the Drosophila tumor suppressor gene warts has implications in the study of the human myotonic dystrophy gene(1). These genes encode (...) members of a cyclic AMP‐dependent protein kinase subfamily that includes other plant and animal orthologues. (shrink)

The up‐ and down‐regulation of the salivary gland secretion protein (Sgs) genes during the third larval instar of Drosophila melanogaster are controlled by fluctuations of the titre of the steroid hormone 20‐hydroxyecdysone (20E). Induction of these genes by a low hormone titre is a secondary response to 20E mediated by products of 20E‐induced ‘early’ genes. Surprisingly, in the case of the Sgs‐4 gene this response also requires a direct contribution of the 20E‐receptor complex. A model is presented which proposes (...) that the Sgs genes, and other 20E‐regulated genes with similar temporal expression profiles, are regulated by complex hormone response units. The hormonal signal is effectively transmitted by these response units only after binding of additional factors, e.g. secretion enhancer binding proteins, which act together in a synergistic manner with the 20E receptor and early gene products to establish a stage‐ and tissuespecific expression pattern. (shrink)

The processes of learning and memory have traditionally been studied in large experimental organisms (Aplysia, mice, rats and humans), where well‐characterized behaviors are easily tested. Although Drosophila is one of the most experimentally tractable organisms, it has only recently joined the others as a model organism for learning and memory. Drosophila behavior has been studied for over 20 years; however, most of the work in the learning and memory field has focused on initial learning, because establishing memory in (...) Drosophila has not been as straightforward as in other organisms. A major recent advance in this field has been the development of a training protocol that induces long‐term memory in flies. This made possible experiments that implicated the Drosophila CREB gene as a critical component in the consolidation of long‐term memory, and paves the way for future experiments utilizing the well developed tools in Drosophila. This review will briefly summarize what is known in the field of Drosophila learning and memory to date, and discuss why the unique aspects of this field make traditional approaches difficult and reward the use of alternative paths of experimentation. (shrink)

The neural correlates of rapid eye movements (REMs) in sleep are extraordinarily robust; including REM-locked activation in the retrosplenial cortex, the supplementary eye field and areas overlapping cholinergic basal nucleus. The phenomenology of REMs speaks to the notion that perceptual experience in both sleep and wakefulness is a constructive process – in which we generate predictions of sensory inputs and then test those predictions through actively sampling the sensorium with eye movements. On this view, REMs during sleep may index an (...) internalized active sampling or ‘scanning’ of self-generated visual constructs that are not constrained by visual input. If this view is correct, it renders REMs an ideal probe to study consciousness as “an exclusively internal affair” (Metzinger 2009). In other words, REMs offer a probe of active inference – in the sense of predictive coding – when the brain is isolated from the sensorium in virtue of the natural blockade of sensory input during REM sleep. REMs are temporally precise events that enable powerful inferences based on timeseries analyses. As a natural, task-free probe, [REMs] could be used in non-compliant subjects, including infants and animals. In short, REM constitutes a promising probe to study the ontogenetic and phylogenetic development of consciousness and perhaps its abnormal development in schizophrenia and autism, which have been considered in terms of aberrant predictive coding. (shrink)

As innovations in the field of vascular composite allotransplantation (VCA) progress, whole-eye transplantation (WET) is poised to transition from non-human mammalian models to living human recipients. Present treatment options for vision loss are generally considered suboptimal, and attendant concerns ranging from aesthetics and prosthesis maintenance to social stigma may be mitigated by WET. Potential benefits to WET recipients may also include partial vision restoration, psychosocial benefits related to identity and social integration, improvements in physical comfort and function, and reduced surgical (...) risk associated with a biologic eye compared to a prosthesis. Perioperative and postoperative risks of WET are expected to be comparable to those of facial transplantation (FT), and may be similarly mitigated by immunosuppressive protocols, adequate psychosocial support, and a thorough selection process for both the recipient and donor. To minimize the risks associated with immunosuppressive medications, the first attempts in human recipients will likely be performed in conjunction with a FT. If first-in-human attempts at combined FT-WET prove successful and the biologic eye survives, this opens the door for further advancement in the field of vision restoration by means of a viable surgical option. This analysis integrates recent innovations in WET research with the existing discourse on the ethics of surgical innovation and offers preliminary guidance to VCA programs considering undertaking WET in human recipients. (shrink)

The formation of the segmentation pattern in Drosophila embryos provides an excellent model for investigating the process of pattern formation in multicellular organisms. Several genes required in an embryo for normal segmentation have been analyzed by classical and molecular genetic and morphological techniques. A detailed consideration of these results suggests that these segmentation genes are combinatorially involved in translating the positional identities of individual cells at an early stage in Drosophila development.