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)

In BioEssays, vol. I. no. 5, p. 227, P. A. Lawrence discussed the selector gene hypothesis and its implications for development. In the following article, D. Gubb presents an alternative view of the genetic control of development.

The imaginal discs of Drosophila melanogaster, which form the adult epidermal structures, are a good experimental model for studying morphogenesis. The genital disc forms the terminalia, which are the most sexually dimorphic structures of the fly. Both sexes of Drosophila have a single genital disc formed by three primordia. The female genital primordium is derived from 8th abdominal segment and is located anteriorly, the anal primordium (10 and 11th abdominal segments) is located posteriorly, and the male genital primordium (...) from the 9th abdominal segment lies between them. In both sexes, only two of these three primordia develop to form the adult terminalia. The anal primordium develops in both sexes but, depending on the genetic sex, will form either male or female analia. However, only one of the genital primordia develops in each sex, forming either the male or the female genitalia. This depends on the genetic sex of the fly. Therefore, the genital disc is a very good experimental model of how the sex‐determination and homeotic genes — which determine cell identity — interact to direct the development of a population of cells into male or female terminalia. It has been proposed that the sexually dimorphic development of the genital disc is the result of an integrated genetic input, made up by the sex‐determination gene doublesex and the homeotic gene Abdominal‐B. This input acts by modulating the response to Hedgehog, Wingless, and Decapentaplegic morphogenetic signals. BioEssays 23:698–707, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The appendages of Drosophila develop from the imaginal discs. During the extensive growth of these discs cell lineages are for the most part unfixed, suggesting a strong role for cell‐cell interactions in controlling the final pattern of differentiation. However, during early and middle stages of development, discs are subdivided by strict lineage restrictions into a small number of spatially distinct compartments. These compartments appear to be maintained by stably inheriting states of gene expression; the compartmentspecific expression of two (...) such ‘selector’ ‐ like genes, engrailed and apterous, are critical for anterior‐posterior and dorso‐ventral compartmentalization, respectively. Recent work suggests that one purpose of compartmentalization is to establish regions of specialized cells near compartment boundaries via intercompartmental induction, using molecules like the hedgehog protein. Thus, compartments can act as organizing centers for patterning within compartments. Evidence for non‐compartmental patterning mechanisms will also be discussed. (shrink)

Glial cells play a central role in the development and function of complex nervous systems. Drosophila is an excellent model organism for the study of mechanisms underlying neural development, and recent attention has been focused on the differentiation and function of glial cells. We now have a nearly complete description of glial cell organization in the embryo, which enables a systematic genetic analysis of glial cell development. Most glia arise from neural stem cells that originate in (...) the neurogenic ectoderm. The bifurcation of glial and neuronal fates is under the control of the glial promoting factor glial cells missing. Differentiation is propagated through the regulation of several transcription factors. Genes have been discovered affecting the terminal differentiation of glia, including the promotion glial–neuronal interactions and the formation of the blood–nerve barrier. Other roles of glia are being explored, including their requirement for axon guidance, neuronal survival, and signaling. BioEssays 23:877–887, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The veins are cuticular structures that differentiate in precise patterns in insect wings. The genetic and molecular basis of vein pattern formation in Drosophila melanogaster is beginning to be unravelled with the identification and characterisation of the gene products that position the veins and direct their differentiation. Genes affecting the veins fall into two groups: transcriptional regulators that specify individual veins, and members of signalling pathways involved in patterning and differentiation of the veins. The elaboration of the vein pattern (...) is progressive in time and requires the coordinated activities of these signalling pathways and the transcription factors regulated by them. Although the network of genetic interactions that determine vein cell fate is well understood, very little is known about the cellular biology underlying the acquisition of vein histotype. BioEssays 25:443–451, 2003. © 2003 Wiley Periodicals, Inc. (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)

The Drosophila embryo provides a useful model system to study the mechanisms that lead to pattern and cell diversity in the central nervous system (CNS). The Drosophila CNS, which encompasses the brain and the ventral nerve cord, develops from a bilaterally symmetrical neuroectoderm, which gives rise to neural stem cells, called neuroblasts. The structure of the embryonic ventral nerve cord is relatively simple, consisting of a sequence of repeated segmental units (neuromeres), and the mechanisms controlling the formation and (...) specification of the neuroblasts that form these neuromeres are quite well understood. Owing to the much higher complexity and hidden segmental organization of the brain, our understanding of its development is still rudimentary. Recent investigations on the expression and function of proneural genes, segmentation genes, dorsoventral‐patterning genes and a number of other genes have provided new insight into the principles of neuroblast formation and patterning during embryonic development of the fly brain. Comparisons with the same processes in the trunk help us to understand what makes the brain different from the ventral nerve cord. Several parallels in early brain patterning between the fly and the vertebrate systems have become evident. BioEssays 26:739–751, 2004. © 2004 Wiley Periodicals, Inc. (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)

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.

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)

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)

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 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)

The identification of network motifs has been widely considered as a significant step towards uncovering the design principles of biomolecular regulatory networks. To date, time‐invariant networks have been considered. However, such approaches cannot be used to reveal time‐specific biological traits due to the dynamic nature of biological systems, and hence may not be applicable to development, where temporal regulation of gene expression is an indispensable characteristic. We propose a concept of a “temporal sequence of network motifs”, a sequence of (...) network motifs in active sub‐networks constructed over time, and investigate significant network motifs in the active temporal sub‐networks of Drosophila melanogaster. Based on this concept, we find a temporal sequence of network motifs which changes according to developmental stages and thereby cannot be identified from the whole static network. Moreover, we show that the temporal sequence of network motifs corresponding to each developmental stage can be used to describe pivotal developmental events. (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 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)

The Drosophila position‐specific (PS) integrins are members of the integrin family of cell surface receptors and are thought to be receptors for extracellular matrix components. Each PS integrin consists of an α subunit, αPS1 or αPS2, and a βPS subunit. Mutations in the βPS subunit and the αPS2 subunit have been characterised and reveal that the PS integrins have an essential role in the adhesion of different cell layers to each other. The PS integrins are especially required for the (...) function of the cell‐matrix‐cell junctions, where the muscles attach to the epidermis and where one surface of the developing wing adheres to the other. These junctions are similar to vertebrate focal adhesions and hemidesmosomes, which also contain integrins. Integrin‐mediated cell to cell adhesion via the extracellular matrix provides a way for tissues to adhere to each other without intermingling of their cells. (shrink)

In Drosophila, the genetic approach is still the method of choice for answering fundamental questions on cell biology, signal transduction, development, physiology and behavior. In this approach, a gene's function is ascertained by altering either the amount or quality of the gene product, and then observing the consequences. The genetic approach is itself polymorphous, encompassing new and more complex techniques that typically employ the growing collections of transgenes. The keystone of these modern Drosophila transgenic techniques has been (...) the Gal4 binary system. Recently, several new techniques have modified this binary system to offer greater control over the timing, tissue specificity and magnitude of gene expression. Additionally, the advances in post‐transcriptional gene silencing, or RNAi, have greatly expanded the ability to knockdown almost any gene's function. Regardless of the growing experimental intricacy, the application of these advances to modify gene activity still obeys the fundamental principles of genetic analysis. Several of these transgenic techniques, which offer more precise control over a gene's activity, will be reviewed here with a discussion on how they may be used for determining a gene's function. BioEssays 26:1243–1253, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The development of organs during animal development requires the allocation of appropriate numbers of cells to each part of the structure. Yet in Drosophila the patterns of cell proliferation can be quite different from one individual to the next, and in fact can be altered experimentally without altering final morphology. The developing pattern seems to control proliferation, rather than the other way around. Even though the pattern of proliferation is variable, there is some order to it. A (...) recent paper(1) shows that small clusters of cells in developing cell populations are in mitotic synchrony, but that the synchrony is transient. What is the significance of this mitotic synchrony? (shrink)

Our understanding of epithelial development in Drosophila has been greatly improved in recent years. Two key regulators of epithelial polarity, Crumbs and DE‐cadherin, have been studied at the genetic and molecular levels and a number of additional genes are being analyzed that contribute to the differentiation of epithelial cell structure. Epithelial architecture has a profound influence on morphogenetic movements, patterning and cell‐type determination. The combination of embryological and genetic/molecular tools in Drosophila will help us to elucidate the (...) complex events that determine epithelial cell structure and how they relate to morphogenesis and other developmental processes. (shrink)

Drosophila melanogaster is often considered to lack genomic 5‐methylcytosine (m5C), an opinion reinforced by two whole genome bisulfite‐sequencing studies that failed to find m5C. New evidence, however, indicates that genomic methylation is indeed present in the fly, albeit in small quantities and in unusual patterns. At embryonic stage 5, m5C occurs in short strand‐specific regions that cover ∼1% of the genome, at tissue levels suggesting a distribution restricted to a subset of nuclei. Its function is not obvious, but methylation (...) in subsets of nuclei would obscure functional associations since transcript levels and epigenetic modifications are assayed in whole embryos. Surprisingly, Mt2, the fly's only candidate DNA methyltransferase, is not necessary for the observed methylation. Full evaluation of the functions of genome methylation in Drosophila must await discovery and experimental inactivation of the DNA methyltransferase, as well as a better understanding of the pattern and developmental regulation of genomic m5C. (shrink)

The 5000 bristles that protrude from the cuticle of a Drosophila adult function as either mechanosensors or chemosensors, and they are arranged in surprisingly intricate patterns. Development of the patterns appears to involve five stages: (1) establishment of a coordinate system of ‘positional information’; (2) partitioning of the epidermis into areas where bristles either can or cannot originate; (3) selection of one or more bristle mother cells within each permissible area; (4) suppression of bristle development in the (...) neighborhood of each mother cell; and (5) differentiation of the mother cell to produce four or more descendant cells, each of which forms part of the bristle apparatus. Some of the genes that control these events participate in more than one stage, and others play key roles in roles in seemingly unrelated developmental pathways, including embryonic neurogenesis, body segmentation, and sex determination. (shrink)

Many sensory processing regions of the central brain undergo critical periods of experience‐dependent plasticity. During this time ethologically relevant information shapes circuit structure and function. The mechanisms that control critical period timing and duration are poorly understood, and this is of special importance for those later periods of development, which often give rise to complex cognitive functions such as social behavior. Here, we review recent findings in Drosophila, an organism that has some unique experimental advantages, and introduce novel (...) views for manipulating plasticity in the post‐embryonic brain. Critical periods in larval and young adult flies resemble classic vertebrate models with distinct onset and termination, display clear connections with complex behaviors, and provide opportunities to control the time course of plasticity. These findings may extend our knowledge about mechanisms underlying extension and reopening of critical periods, a concept that has great relevance to many human neurodevelopmental disorders. (shrink)

Neuronal remodeling is a conserved mechanism that eliminates unwanted neurites and can include the loss of cell bodies. In these processes, a key role for glial cells in events from synaptic pruning to neuron elimination has been clearly identified in the last decades. Signals sent from dying neurons or neurites to be removed are received by appropriate glial cells. After receiving these signals, glial cells infiltrate degenerating sites and then, engulf and clear neuronal debris through phagocytic mechanisms. There are few (...) identified or proposed signals and receptors involved in neuron‐glia crosstalk, which induces the transformation of glial cells to phagocytes during neuronal remodeling in Drosophila. Many of these signaling pathways are conserved in mammals. Here, we particularly emphasize the role of Orion, a recently identified neuronal CX3C chemokine‐like secreted protein, which induces astrocyte infiltration and engulfment during mushroom body neuronal remodeling. Although, chemokine signaling was not described previously in insects we propose that chemokine‐like involvement in neuron/glial cell interaction is an evolutionarily ancient mechanism. (shrink)

The Transforming growth factor beta (TGF‐β) family of secreted proteins regulates a variety of key events in normal development and physiology. In mammals, this family, represented by 33 ligands, including TGF‐β, activins, nodal, bone morphogenetic proteins (BMPs), and growth and differentiation factors (GDFs), regulate biological processes as diverse as cell proliferation, differentiation, apoptosis, metabolism, homeostasis, immune response, wound repair, and endocrine functions. In Drosophila, only 7 members of this family are present, with 4 TGF‐β/BMP and 3 TGF‐β/activin ligands. (...) Studies in the fly have illustrated the role of TGF‐β/BMP ligands during embryogenesis and organ patterning, while the TGF‐β/activin ligands have been implicated in the control of wing growth and neuronal functions. In this review, we focus on the emerging roles of Drosophila TGF‐β/activins in inter‐organ communication via long‐distance regulation, especially in systemic lipid and carbohydrate homeostasis, and discuss findings relevant to metabolic diseases in humans. -/- . (shrink)

The development of vertebrate and invertebrate nervous systems requires the production of thousands to millions of uniquely specified neurons from progenitor neural stem cells. A central question focuses on the elucidation of the developmental mechanisms that function within neural stem cell lineages to impart unique identities to neurons. A recent report(1) details the roles that two genes, pdm‐1 and pdm‐2, play within an identified neural stem cell lineage in the Drosophila embryonic central nervous system. The results show that (...) pdm‐1 and pdm‐2 are coexpressed in an identified neural precursor and function redundantly to specify the fate of this cell. As such this report offers an initial view of the genetic programs that create neural diversity. (shrink)

The evolutionarily conserved Notch signaling pathway regulates a broad spectrum of cell fate decisions and differentiation processes during fetal and postnatal life. It is involved in embryonic organogenesis as well as in the maintenance of homeostasis of self‐renewing systems. In this article, we review the role of Notch signaling in the hematopoietic system with particular emphasis on lymphocyte development and highlight the similarities in Notch function between Drosophila and mammalian differentiation processes. Recent studies indicating that aberrant NOTCH signaling (...) is frequently linked to the induction of T leukemia in humans will also be discussed. BioEssays 27:1117–1128, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Embryonic development in Drosophila melanogaster begins with a rapid series of mitotic nuclear divisions, unaccompanied by cytokinesis, to produce a multi‐nucleated single cell embryo, the syncytial blastoderm. The syncytium then undergoes a process of cell formation, in which the individual nuclei become enclosed in individual cells. This process of cellularization involves integrating mechanisms of cell polarity, cell–cell adhesion and a specialized form of cytokinesis. The detailed molecular mechanism, however, is highly complex and, despite extensive analysis, remains poorly understood. (...) Nevertheless, new insights are emerging from recent studies on aspects of membrane polarization and insertion, which show that membrane components from intracellular organelles are involved. In addition, actin and actin‐associated proteins have been heavily implicated while new evidence shows that microtubule cytoskeletal elements are mechanistically involved in all aspects of cellularization. This review will draw on both the traditional models and the new data to provide a current perspective on the nature of cellular blastoderm formation in Drosophila melanogaster. BioEssays 24:1012–1022, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

The specification of specific and often unique fates to individual cells as a function of their position within a developing organism is a fundamental process during the development of multicellular organisms. The development of the Drosophila embryonic central nervous system serves as an excellent model system in which to clarify the developmental mechanisms that link pattern formation to cell-type specification. The Drosophila embryonic central nervous system develops from a set of neural stem cells termed neuroblasts. Neuroblasts (...) arise from the ectoderm in an invariant pattern, and each neuroblast acquires a unique fate based on its position within this pattern. Two groups of genes recently have been demonstrated to govern the individual fate specification of neuroblasts. One group, the segment polarity genes, enables neuroblasts that develop in different anteroposterior positions to acquire different fates. The second group, referred to as the columnar genes, ensures that neuroblasts that develop in different dorsoventral domains assume different fates. When integrated, the activities of the segment polarity and columnar genes create a Cartesian coordinate system that bestows unique fates to individual neuroblasts as a function of their position of formation within the ectoderm. BioEssays 1999;21:922–931. © 1999 John Wiley & Sons, Inc. (shrink)

The cuticular surface of Drosophila is decorated by parallel arrays of polarized structures such as hairs and sensory bristles; for example, on the wing each cell produces a distally pointing hair. These patterns are termed [tissue polarity]. Several genes are known whose activity is essential for the development of normal tissue polarity. Mutations in these genes alter the orientation of the hair or bristle with respect to neighboring cells and the body as a whole. The phenotypes of mutations (...) in these genes allows them to be placed in three phenotypic groups. Based on their behavior in genetic mosaics, it has proved possible to determine that individual genes are required either for the generation of an intercellular polarity signal and/or the transduction of that signal to the cytoskeleton. (shrink)

The specification of specific and often unique fates to individual cells as a function of their position within a developing organism is a fundamental process during the development of multicellular organisms. The development of the Drosophila embryonic central nervous system serves as an excellent model system in which to clarify the developmental mechanisms that link pattern formation to cell-type specification. The Drosophila embryonic central nervous system develops from a set of neural stem cells termed neuroblasts. Neuroblasts (...) arise from the ectoderm in an invariant pattern, and each neuroblast acquires a unique fate based on its position within this pattern. Two groups of genes recently have been demonstrated to govern the individual fate specification of neuroblasts. One group, the segment polarity genes, enables neuroblasts that develop in different anteroposterior positions to acquire different fates. The second group, referred to as the columnar genes, ensures that neuroblasts that develop in different dorsoventral domains assume different fates. When integrated, the activities of the segment polarity and columnar genes create a Cartesian coordinate system that bestows unique fates to individual neuroblasts as a function of their position of formation within the ectoderm. BioEssays 1999;21:922–931. © 1999 John Wiley & Sons, Inc. (shrink)

Sex determination in the germ line may either rely on cell‐autonomous genetic information, or it may be imposed during development by inductive somatic signals. In Drosophila, both mechanisms contribute to ensure that germ cells are oogenic when differentiating in females and spermatogenic when differentiating in males. Some of the genes that are involved in germ line sex determination have been identified. In other species, including vertebrates, inductive signals are commonly used to determine the sex of germ cells.

In many animals, early development of the embryo is characterized by synchronous, biphasic cell divisions. These cell divisions are controlled by maternally inherited proteins and RNAs. A critical question in developmental biology is how the embryo transitions to a later pattern of asynchronous cell divisions and transfers the prior maternal control of development to the zygotic genome. The most‐common model regarding how this transition from maternal to zygotic control is regulated posits that this is a consequence of the (...) limitation of maternal gene products, due to their titration during early cell divisions. Here we discuss a recent article by Crest et al.1 that instead proposes that the balance of Cyclin‐dependent Kinase 1 and Cyclin B (Cdk1‐CycB) activity relative to that of the Drosophila checkpoint kinase Chk1 determines when asynchronous divisions begin. BioEssays 29:949–952, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Development and homeostasis of the haematopoietic system is dependent upon stem cells that have the unique ability to both self‐renew and to differentiate in all cell lineages of the blood. The crucial decision between haematopoietic stem cell (HSC) self‐renewal and differentiation must be tightly controlled. Ultimately, this choice is regulated by the integration of intrinsic signals together with extrinsic cues provided by an exclusive microenvironment, the so‐called haematopoietic niche. Although the haematopoietic system of vertebrates has been studied extensively for (...) many decades, the specification of the HSC niche and its signals involved are poorly understood. Much of our current knowledge of how niches regulate long‐term maintenance of stem cells is derived from studies on Drosophila germ cells. Now, two recently published studies by Mandal et al.1 and Krezmien et al.2 describe the Drosophila haematopoietic niche and signal transduction pathways that are involved in the maintenance of haematopoietic precursors. Both reports emphasize several features that are important for controlling stem cell behavior and show parallels to both the vertebrate haematopoietic niche as well as the Drosophila germline stem cell niches in ovary and testis. The findings of both papers shed new light on the specific interactions between haematopoietic progenitors and their microenvironment. BioEssays 29:713–716, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Targeting of cell ablation agents under the control of tissue‐specific promoters promises to be an important tool for studies of development and function in higher organisms. Temperature‐sensitive cell ablation agents, recently developed for Drosophila, extend control to temporal as well as spatial aspects of toxin expression. Here we discuss achievements to date, together with a novel form of enhancer trap technology with the potential for driving toxin expression in a large range of cell types.

Transplantation experiments have shown that developing metazoan organs carry intrinsic information about their size and shape. Organ and body size are also sensitive to extrinsic cues provided by the environment, such as the availability of nutrients. The genetic and molecular pathways that contribute to animal size and shape are numerous, yet how they cooperate to control growth is mysterious. The recent identification and characterization of several mutations affecting growth in Drosophila melanogaster promises to provide insights. Many of these mutations (...) affect the extrinsic control of animal size; others affect the organ‐intrinsic control of pattern and size. In this review, we summarize the characteristics of some of these mutations and their roles in growth and size control. In addition, we speculate about possible connections between the extrinsic and intrinsic pathways controlling growth and pattern. BioEssays 24:54–64, 2002. © 2002 John Wiley & Sons, Inc. (shrink)

The growing number of cloned eukaryotic genes lacking a defined or proven biological function poses a major challenge in ‘reverse genetics’. A method is described here that permits efficient screening for new lesions in, or close to, genes corresponding to cloned DNA sequences of interest. The technique involves transposon mutagenesis, followed by screening of DNA isolated from a population of mutagenised individuals (or their progeny) for evidence that the population contains at least one individual in which transposon insertion has occurred (...) at the target locus. Detection of rare individuals within the population is facilitated by the use of the polymerase chain reaction (PCR). Once recognised, specific individuals (or their progeny) are isolated from the population by a process of sib‐selection. In cases where insertion of the transposon has occurred close to, but not within, the target locus, secondary events involving imprecise excision of the transposon will nonetheless allow the isolation of mutant individuals. Though the method was developed specifically for the transposon‐mutagenesis of Drosophila, extensions to other organisms and to other mutagenic strategies are feasible and some of the possibilities are discussed. (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)

Most characters that distinguish one individual from another, like height or weight, vary continuously in populations. Continuous variation of these ‘quantitative’ traits is due to the simultaneous segregation of multiple quantitative trait loci (QTLs) as well as environmental influences. A major challenge in human medicine, animal and plant breeding and evolutionary genetics is to identify QTLs and determine their genetic properties. Studies of the classic quantitative traits, abdominal and sternopleural bristle numbers of Drosophila, have shown that: (1) many loci (...) have small effects on bristle number, but a few have large effects and cause most of the genetic variation; (2) ‘candidate’ loci involved in bristle development often have large quantitative effects on bristle number; and (3) alleles at QTLs affecting bristle number have variable degrees of dominance, interact with each other, and affect other quantitative traits, including fitness. Lessons learned from this model system will be applicable to studies of the genetic basis of quantitative variation in other species. (shrink)