achaete and scute are expressed in a spatially restricted pattern and provide neural potential to... more achaete and scute are expressed in a spatially restricted pattern and provide neural potential to cells, rhe domains of expression depend partly on extra- macrochaetae whose product is itself spatially restricted and acts as a negative post-translational regulator of achaete and scute. The protein kinase shaggy also represses achaete and scute at many sites hut may act via intermediate transcription factors. However shaggy and extramacrochaetae act synergistically and molecular studies suggest that they may be part of the same pathway, shaggy is functionally homologous to the mammalian glycogen synthase kinase-3 and analogy with the known physiology of this enzyme, suggests that this function of shaggy may result from the “constitu- tive” activity. At the site where a single neural precursor will develop, achaete and scute are initially expressed in a group of equivalent cells. ‘Hie genes Notch and Delta are part of a lateral signal required to single out one precursor cell and to s...
Signaling by the secreted hedgehog, decapentaplegic and wingless proteins organizes the pattern o... more Signaling by the secreted hedgehog, decapentaplegic and wingless proteins organizes the pattern of photoreceptor differentiation within the Drosophila eye imaginal disc; hedgehog and decapentaplegic are required for differentiation to initiate at the posterior margin and progress across the disc, while wingless prevents it from initiating at the lateral margins. Our analysis of these interactions has shown that initiation requires both the presence of decapentaplegic and the absence of wingless, which inhibits photoreceptor differentiation downstream of the reception of the decapentaplegic signal. However, wingless is unable to inhibit differentiation driven by activation of the epidermal growth factor receptor pathway. The effect of wingless is subject to regional variations in control, as the anterior margin of the disc is insensitive to wingless inhibition. The eyes absent and eyegone genes encode members of a group of nuclear proteins required to specify the fate of the eye imag...
Like the neuroblasts of the central nervous system, sensory organ precursors of the peripheral ne... more Like the neuroblasts of the central nervous system, sensory organ precursors of the peripheral nervous system of the Drosophila thorax arise as single spaced cells. However, groups of cells initially have neural potential as visualized by the expression of the proneural genes achaete and scute. A class of genes, known as the ‘neurogenic genes’, function to restrict the proportion of cells that differentiate as sensory organ precursors. They mediate cell communication between the competent cells by means of an inhibitory signal, Delta, that is transduced through the Notch receptor and results in a cessation of achaete-scute activity. Here we show that mutation of either the bHLH-encoding genes of the Enhancer of split complex (E(spl)-C) or groucho, like Notch or Delta mutants, cause an overproduction of sensory organ precursors at the expense of epidermis. The mutant cells behave autonomously suggesting that the corresponding gene products are required for reception of the inhibitory...
Early studies of glycogen synthase kinase 3 (GSK-3) in mammalian systems focused on its pivotal r... more Early studies of glycogen synthase kinase 3 (GSK-3) in mammalian systems focused on its pivotal role in glycogen metabolism and insulin-mediated signaling. It is now recognized that GSK-3 is central to a number of diverse signaling systems. Here, we show that the major form of the kinase Shaggy (Sgg), the GSK-3 fly ortholog, is negatively regulated during insulin-like/phosphatidylinositol 3-kinase (PI3K) signaling in vivo. Since genetic studies of Drosophila melanogaster had previously shown that Wingless (Wg) signaling also acts to antagonize Sgg, we investigate how the kinase might integrate, or else discriminate, signaling inputs by Wg and insulin. Using Drosophila cell line assays, we found, in contrast to previous reports, that Wg induces accumulation of its transducer Armadillo (Arm)/β-catenin without significant alteration of global Sgg-specific activity. In agreement with a previous study using human GSK-3β, Wg did not cause phosphorylation changes of the Ser9 or Tyr214 regu...
The pattern of the large sensory bristles on the notum ofDrosophila arises as a consequence of th... more The pattern of the large sensory bristles on the notum ofDrosophila arises as a consequence of the expression of theachaete and scute genes. The gene u-shapedencodes a novel zinc finger that acts as a transregulator ofachaete and scute in the dorsal region of the notum. Viable hypomorphic u-shaped mutants display additional dorsocentral and scutellar bristles that result from overexpression ofachaete and scute. In contrast, overexpression ofu-shaped causes a loss of achaete–scute expression and consequently a loss of dorsal bristles. The effects on the dorsocentral bristles appear to be mediated through the enhancer sequences that regulate achaete and scute at this site. The effects ofu-shaped mutants are similar to those of a class of dominant alleles of the gene pannier with which they display allele-specific interactions, suggesting that the products of both genes cooperate in the regulation of achaete and scute.A study of the sites at which the dorsocentral bristles arise in mos...
Insulin signaling is a conserved feature in all metazoans. It evolved with the appearance of mult... more Insulin signaling is a conserved feature in all metazoans. It evolved with the appearance of multicellularity, allowing primordial metazoans to respond to a greater diversity of environmental signals. The insulin signaling pathway is highly conserved in insects and particularly in Drosophila, where it has been extensively studied in recent years and shown to control metabolism, growth, reproduction, and longevity. Because misregulation of the insulin/IGF pathway in humans plays a role in many medical disorders, such as diabetes and various types of cancer, unraveling the regulation of insulin/IGF signaling using the power of a genetically tractable organism like Drosophila may contribute to the amelioration of these major human pathologies.
Cold Spring Harbor Symposia on Quantitative Biology, 1992
In most invertebrates, the neural precursors for both central and peripheral nervous ystems arise... more In most invertebrates, the neural precursors for both central and peripheral nervous ystems arise in a spaced pattern and are separated by intervening epidermal cells. Each precursor has a unique identity thought o be dependent on the position in the epithelium atwhich it is born (Taghert et al. 1984; Doe and Goodman, 1985; Doe et al. 1988a,b; Patel et al. 1989). Each precursor produces adefined set of specific neurons in a remarkably stereotyped array (Bate 1976). The genera-tion of spaced precursors f om a large area of the embryo may be a means of allowing the segregation of a large number of cells, each with a different positional identity. This mode of development means that an individual cell, the precursor, adopts a fate that is different from that of each of its neighboring cells.
Data are presented of electron microscopic (EM) analysis of consecutive developmental stages of D... more Data are presented of electron microscopic (EM) analysis of consecutive developmental stages of Drosophila melanogaster complex puffs, formed as a result of simultaneous decondensation of several bands. EM mapping principles proposed by us permitted more exact determination of the banding patterns of 19 regions in which 31 puffs develop. It is shown that 20 of them develop as a result
In the preparation of this manuscript, we have erroneously translated the experimental results of... more In the preparation of this manuscript, we have erroneously translated the experimental results of our glucose measurement into final hemolymph concentrations. The legend on the y axis in the graphs shown in Figures and should read ''Glucose (g/dl)'' instead of ''Glucose (mg/ml).'' The corrections do not change the conclusions in the paper, and we apologize for any confusion the errors might have caused.
achaete and scute are expressed in a spatially restricted pattern and provide neural potential to... more achaete and scute are expressed in a spatially restricted pattern and provide neural potential to cells, rhe domains of expression depend partly on extra- macrochaetae whose product is itself spatially restricted and acts as a negative post-translational regulator of achaete and scute. The protein kinase shaggy also represses achaete and scute at many sites hut may act via intermediate transcription factors. However shaggy and extramacrochaetae act synergistically and molecular studies suggest that they may be part of the same pathway, shaggy is functionally homologous to the mammalian glycogen synthase kinase-3 and analogy with the known physiology of this enzyme, suggests that this function of shaggy may result from the “constitu- tive” activity. At the site where a single neural precursor will develop, achaete and scute are initially expressed in a group of equivalent cells. ‘Hie genes Notch and Delta are part of a lateral signal required to single out one precursor cell and to s...
Signaling by the secreted hedgehog, decapentaplegic and wingless proteins organizes the pattern o... more Signaling by the secreted hedgehog, decapentaplegic and wingless proteins organizes the pattern of photoreceptor differentiation within the Drosophila eye imaginal disc; hedgehog and decapentaplegic are required for differentiation to initiate at the posterior margin and progress across the disc, while wingless prevents it from initiating at the lateral margins. Our analysis of these interactions has shown that initiation requires both the presence of decapentaplegic and the absence of wingless, which inhibits photoreceptor differentiation downstream of the reception of the decapentaplegic signal. However, wingless is unable to inhibit differentiation driven by activation of the epidermal growth factor receptor pathway. The effect of wingless is subject to regional variations in control, as the anterior margin of the disc is insensitive to wingless inhibition. The eyes absent and eyegone genes encode members of a group of nuclear proteins required to specify the fate of the eye imag...
Like the neuroblasts of the central nervous system, sensory organ precursors of the peripheral ne... more Like the neuroblasts of the central nervous system, sensory organ precursors of the peripheral nervous system of the Drosophila thorax arise as single spaced cells. However, groups of cells initially have neural potential as visualized by the expression of the proneural genes achaete and scute. A class of genes, known as the ‘neurogenic genes’, function to restrict the proportion of cells that differentiate as sensory organ precursors. They mediate cell communication between the competent cells by means of an inhibitory signal, Delta, that is transduced through the Notch receptor and results in a cessation of achaete-scute activity. Here we show that mutation of either the bHLH-encoding genes of the Enhancer of split complex (E(spl)-C) or groucho, like Notch or Delta mutants, cause an overproduction of sensory organ precursors at the expense of epidermis. The mutant cells behave autonomously suggesting that the corresponding gene products are required for reception of the inhibitory...
Early studies of glycogen synthase kinase 3 (GSK-3) in mammalian systems focused on its pivotal r... more Early studies of glycogen synthase kinase 3 (GSK-3) in mammalian systems focused on its pivotal role in glycogen metabolism and insulin-mediated signaling. It is now recognized that GSK-3 is central to a number of diverse signaling systems. Here, we show that the major form of the kinase Shaggy (Sgg), the GSK-3 fly ortholog, is negatively regulated during insulin-like/phosphatidylinositol 3-kinase (PI3K) signaling in vivo. Since genetic studies of Drosophila melanogaster had previously shown that Wingless (Wg) signaling also acts to antagonize Sgg, we investigate how the kinase might integrate, or else discriminate, signaling inputs by Wg and insulin. Using Drosophila cell line assays, we found, in contrast to previous reports, that Wg induces accumulation of its transducer Armadillo (Arm)/β-catenin without significant alteration of global Sgg-specific activity. In agreement with a previous study using human GSK-3β, Wg did not cause phosphorylation changes of the Ser9 or Tyr214 regu...
The pattern of the large sensory bristles on the notum ofDrosophila arises as a consequence of th... more The pattern of the large sensory bristles on the notum ofDrosophila arises as a consequence of the expression of theachaete and scute genes. The gene u-shapedencodes a novel zinc finger that acts as a transregulator ofachaete and scute in the dorsal region of the notum. Viable hypomorphic u-shaped mutants display additional dorsocentral and scutellar bristles that result from overexpression ofachaete and scute. In contrast, overexpression ofu-shaped causes a loss of achaete–scute expression and consequently a loss of dorsal bristles. The effects on the dorsocentral bristles appear to be mediated through the enhancer sequences that regulate achaete and scute at this site. The effects ofu-shaped mutants are similar to those of a class of dominant alleles of the gene pannier with which they display allele-specific interactions, suggesting that the products of both genes cooperate in the regulation of achaete and scute.A study of the sites at which the dorsocentral bristles arise in mos...
Insulin signaling is a conserved feature in all metazoans. It evolved with the appearance of mult... more Insulin signaling is a conserved feature in all metazoans. It evolved with the appearance of multicellularity, allowing primordial metazoans to respond to a greater diversity of environmental signals. The insulin signaling pathway is highly conserved in insects and particularly in Drosophila, where it has been extensively studied in recent years and shown to control metabolism, growth, reproduction, and longevity. Because misregulation of the insulin/IGF pathway in humans plays a role in many medical disorders, such as diabetes and various types of cancer, unraveling the regulation of insulin/IGF signaling using the power of a genetically tractable organism like Drosophila may contribute to the amelioration of these major human pathologies.
Cold Spring Harbor Symposia on Quantitative Biology, 1992
In most invertebrates, the neural precursors for both central and peripheral nervous ystems arise... more In most invertebrates, the neural precursors for both central and peripheral nervous ystems arise in a spaced pattern and are separated by intervening epidermal cells. Each precursor has a unique identity thought o be dependent on the position in the epithelium atwhich it is born (Taghert et al. 1984; Doe and Goodman, 1985; Doe et al. 1988a,b; Patel et al. 1989). Each precursor produces adefined set of specific neurons in a remarkably stereotyped array (Bate 1976). The genera-tion of spaced precursors f om a large area of the embryo may be a means of allowing the segregation of a large number of cells, each with a different positional identity. This mode of development means that an individual cell, the precursor, adopts a fate that is different from that of each of its neighboring cells.
Data are presented of electron microscopic (EM) analysis of consecutive developmental stages of D... more Data are presented of electron microscopic (EM) analysis of consecutive developmental stages of Drosophila melanogaster complex puffs, formed as a result of simultaneous decondensation of several bands. EM mapping principles proposed by us permitted more exact determination of the banding patterns of 19 regions in which 31 puffs develop. It is shown that 20 of them develop as a result
In the preparation of this manuscript, we have erroneously translated the experimental results of... more In the preparation of this manuscript, we have erroneously translated the experimental results of our glucose measurement into final hemolymph concentrations. The legend on the y axis in the graphs shown in Figures and should read ''Glucose (g/dl)'' instead of ''Glucose (mg/ml).'' The corrections do not change the conclusions in the paper, and we apologize for any confusion the errors might have caused.
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