Yuko Shimada-Niwa

• PhD
• Professor (Assistant) at University of Tsukuba

Parasitoid wasps, one of the most diverse and species-rich animal groups on Earth, produce venoms that manipulate host development and physiology to exploit resources. However, mechanisms of actions of these venoms remain poorly understood. Here, we discovered that the endoparasitoid wasp, Asobara japonica , induces apoptosis, autophagy, and mitoti...

Parasitoid wasps, one of the most diverse and species-rich animal taxa on Earth, produce venoms that manipulate host development and physiology to exploit host resources. However, mechanisms of venom action remain poorly understood. Here, we show that infection of host Drosophila by the endoparasitoid wasp, Asobara japonica , triggers imaginal disc...

Asobara japonica is an endoparasitic wasp that parasitizes Drosophila flies. It synthesizes various toxic components in the venom gland and injects them into host larvae during oviposition. To identify and characterize these toxic components for enabling parasitism, we performed the whole-genome sequencing (WGS) and devised a protocol for RNA inter...

A new study reveals that Drosophila insulin-like peptides (Dilps) accumulate in adipokinetic hormone (AKH)-producing cells in a manner dependent on the insulin-binding protein ImpL2. Under nutrient limitation, AKH and Dilps are released from these cells, maintaining the local tissue-specific activation of insulin signaling in steroidogenic organs a...

The corpora allata (CA) are essential endocrine organs that biosynthesize and secrete the sesquiterpenoid hormone, namely juvenile hormone (JH), to regulate a wide variety of developmental and physiological events in insects. CA are directly innervated with neurons in many insect species, implying the innervations to be important for regulating JH...

The corpora allata (CA) are essential endocrine organs that biosynthesize and secrete the sesquiterpenoid hormone, namely juvenile hormone (JH), to regulate a wide variety of developmental and physiological events in insects. Previous studies had demonstrated that the CA are directly innervated with neurons in many insect species, implying the inne...

Here, we have developed DIAMonDS ( Drosophila Individual Activity Monitoring and Detection System) comprising time-lapse imaging by a charge-coupled device (CCD) flatbed scanner and Sapphire, a novel algorithm and web application. DIAMonDS automatically and sequentially identified the transition time points of multiple life cycle events such as pup...

Stem cells fuel the development and maintenance of tissues. Many studies have addressed how local signals from neighboring niche cells regulate stem cell identity and their proliferative potential. However, the regulation of stem cells by tissue-extrinsic signals in response to environmental cues remains poorly understood. Here we report that effer...

Stem cells fuel the development and maintenance of tissues. Many studies have addressed how local signals from neighboring niche cells regulate stem cell identity and their proliferative potential. However, the regulation of stem cells by tissue-extrinsic signals in response to environmental cues remains poorly understood. Here we report that effer...

Stem cells fuel the development and maintenance of tissues. Many studies have addressed how local signals from neighboring niche cells regulate stem cell identity and their proliferative potential. However, the regulation of stem cells by tissue-extrinsic signals in response to environmental cues remains poorly understood. Here we report that effer...

Here, we have developed DIAMonDS (Drosophila Individual Activity Monitoring and Detection System) comprising time-lapse imaging by a charge-coupled device (CCD) flatbed scanner and Sapphire, a novel algorithm and web application. DIAMonDS automatically and sequentially identified the transition time points of multiple life cycle events such as pupa...

Steroid hormones play key roles in development, growth, and reproduction in various animal phyla [1]. The insect steroid hormone, ecdysteroid, coordinates growth and maturation, represented by molting and metamorphosis [2]. In Drosophila melanogaster, the prothoracicotropic hormone (PTTH)-producing neurons stimulate peak levels of ecdysteroid biosy...

Ecdysteroids are the principal steroid hormones essential for insect development and physiology. In the last 18 years, several enzymes responsible for ecdysteroid biosynthesis encoded by Halloween genes were identified and genetically and biochemically characterized. However, the tertiary structures of these proteins have not yet been characterized...

Stem cells fuel the development and maintenance of tissues. Many studies have addressed how local signals from neighboring niche cells regulate stem cell identity and their proliferative potential. However, the regulation of stem cells by tissue-extrinsic signals in response to external cues remains poorly understood. Here we report that efferent o...

Ecdysteroids are the principal insect steroid hormones essential for insect development and physiology. In the last 18 years, several enzymes responsible for ecdysteroid biosynthesis, encoded by Halloween genes, have been identified and well characterized, both genetically and biochemically. However, none of these proteins have yet been characteriz...

Stem cell maintenance is established by neighboring niche cells that promote stem cell self-renewal. However, it is poorly understood how stem cell activity is regulated by systemic, tissue-extrinsic signals in response to environmental cues and changes in physiological status. Here, we show that neuropeptide F (NPF) signaling plays an important ro...

NPF localization in the brain and midgut. (A, B) Representative images of adult female brains and midguts immunostained with anti-NPF antibody (green) and monoclonal nc82 (neuropil marker; magenta) or phalloidin (magenta). Anti-NPF signals in neuroendocrine cells (arrowhead) were dramatically reduced by loss of NPF (panel A) or neuronal knockdown o...

Expression pattern of Tk-gut-GAL4 driver. (A–C) Representative images of adult female brains and midguts immunostained with anti-NPF antibody (green) or anti-GFP antibody (green) and monoclonal nc82 (neuropil marker; magenta) or phalloidin (magenta). (A, B) Tkg-GAL4 driver expressed in the brain and VNC but not in the ovary. (C) NPF RNAi driven by...

Neuronal or intestinal NPFR does not regulate the mating-induced increase in GSC number. (A) Representative images of adult female brains, VNCs, and midguts immunostained with anti-GFP antibody (green) and monoclonal nc82 (neuropil marker; magenta) or phalloidin (magenta) in c587-GAL4>mCD::GFP or tj-GAL4>mCD8::GFP females. Both GAL4 drivers are exp...

SP signaling controls NPF accumulation in midgut EECs. (A, C) Representative images of anti-NPF antibody immunostaining in the middle midgut are shown on the left. Quantification of anti-NPF signal intensity in the middle midgut is shown on the right graph. Anti-NPF signal intensity did not change after overexpressing membrane-thethered SP (mSP) in...

Underlying data for main and supporting figures. In this file, separate worksheets contain the data used in each figure panel as indicated. (XLSX)

Expression pattern of several EEC-GAL4 drivers. Representative images of adult female brains and midguts immunostained with anti-GFP antibody (green), anti-NPF antibody (magenta), or phalloidin (magenta). These GAL4 drivers were expressed in NPF-positive EECs. Anti-GFP signals were also detected in the brain, VNC, and oviduct, but not the ovary. Sc...

Gut NPF is not involved in gut remodeling. (A, B) The number of mitotic cells (panel A) or size (panel B) of the posterior midgut in virgin or mated female flies was not affected by NPF RNAi driven by Tkg-GAL4 (NPF-positive EECs). (C) Frequency of germaria containing 1, 2, and 3 GSCs (left axis) and the average number of GSCs per germarium (right a...

NPF-dependent increase in GSC number requires ovarian ecdysteroid signaling. (A) Ecdysteroid levels in mated ovaries did not change in Tkg-GAL4>NPFRNAi animals. (B, C) Frequency of germaria containing 1, 2, and 3 GSCs (left axis) and the average number of GSCs per germarium (right axis) in virgin (v) and mated (m) female flies. (B) GSC phenotype in...

Ecdysteroids, including the biologically active hormone 20-hydroxyecdysone (20E), play essential roles in controlling many developmental and physiological events in insects. Ecdysteroid biosynthesis is achieved by a series of specialized enzymes encoded in the Halloween genes. Recently, a new class of Halloween gene, noppera-bo (nobo), encoding a g...

In multicellular organisms, a small group of cells is endowed with a specialized function in their biogenic activity, inducing a systemic response to growth and reproduction. In insects, the larval prothoracic gland (PG) and the adult female ovary play essential roles in biosynthesizing the principal steroid hormones called ecdysteroids. These ecdy...

Transcription factors generally regulate gene expression of multiple targets. In contrast, our recent finding suggests that the zinc finger protein Ouija board controls steroid hormone biosynthesis through specific regulation of only one gene spookier in Drosophila. It sheds light on a specialized but essential factor that evolved for one target.

The developmental transition from juvenile to adult is often accompanied by many systemic changes in morphology, metabolism, and reproduction. Curiously, both mammalian puberty and insect metamorphosis are triggered by a pulse of steroid hormones, which can harmonize gene expression profiles in the body and thus orchestrate drastic biological chang...

Steroid hormones are crucial for many biological events in multicellular organisms. In insects, the principal steroid hormones are ecdysteroids, which play essential roles in regulating molting and metamorphosis. During larval and pupal development, ecdysteroids are synthesized in the prothoracic gland (PG) from dietary cholesterol via a series of...

Drosophilidae orthologs of ouija board. The orthologs of ouija board in 12 Drosophilidae species are described in the FlyBase website (http://flybase.org/reports/FBgn0209782.html). We confirmed by the BLAST search that the amino acid sequence of any of these putative proteins as a query is most similar to that of D. melanogaster CG11762. (PDF)

Rescue of spok RNAi animals by spo overexpression in the PG. The number of spok RNAi animals that grew up to the 3rd instar larval stage or later stage was scored. Detailed genetic crosses for this experiment are described in Materials and Methods. The animals were fed standard cornmeal food without any steroidal supplements. Values in parentheses...

The genomic structure of ouija board (CG11762) and surrounding genes. The data are derived from the FlyBase GBrowse website (http://flybase.org/cgi-bin/gbrowse2/dmel/?Search=1;name=FBgn0037618). Numbers indicate the nucleotide positions at the 85A9 cytological position of the chromosome 3R scaffold. Boxed arrows represent gene spans and their direc...

Sequences similar to Ouib-response element in putative enhancers/promoters of ecdysteroidogenic genes in D. melanogaster. EMBOSS Matcher [54] was used to search for sequences similar to D. melanogaster Ouib response element (15 bp) within the putative enhancer/promoter regions of D. melanogaster ecdysteroidogenic enzyme genes. Numbers before and af...

RNA in situ hybridization using embryos with antisense and sense ouib RNA probes. Dorsal views are shown. (A) Signals with antisense probe. (B) Signals with sense probe. Arrows indicate positions of the PG primordia. Scale bar: 100 μm. (PDF)

GFP expression driven by the spok enhancer. (A, B) Phase-contrast (left) and fluorescence (right) images of the 108 hours AEL 3rd instar larval brain-ring gland complexes with spok>GFP construct. The PG cells were immunostained with anti-Sro antibody (magenta). The spok>GFP constructs contain 1.45 kbp (A) and 300 bp (B) enhancer regiosn of spok, re...

Luciferase reporter assay with plasmids containing the series of upstream elements of spok. Numbers indicate the distance from the translation initiation site (+1) of spok, and white box represents the coding region of spok. Luc reporter activities of progressive deletion constructs are shown in right. Bars and error bars represent the average and...

Expression level of ouib in the PGs of control and torso RNAi third instar larvae. Amounts of ouib mRNAs were measured by qRT-PCR. phm>+ and phm>torso-IR indicate w 1118 ; +/+; phm-GAL4#22/+ and w 1118 ; UAS-torso-IR/+; phm-GAL4#22/+, respectively. RNA samples were collected 140 hours after egg laying. Bars and error bars represent the average and...

List of primers/oligonucleotide DNAs used in this study. Small letters indicate the restriction enzyme recognition sequences. Under lines indicate the transversion mutation sequences. Asterisks indicate 5´ biotinylation. (PDF)

Luciferase reporter assay with plasmids containing the triplet transversion mutations in the -166 to -152 region of the 300 bp upstream element of spok. The introduced transversion mutations in the 1’, 2’, 3’, 4’ and 5’ constructs are shown in the top. The GFP expression plasmid was used as a negative control. Bars and error bars represent the aver...

Expression level of spok and ouib in the PGs of control and mld RNAi first instar larvae. Amounts of spok and ouib mRNAs were measured by qRT-PCR. phm>dicer2 and phm>dicer2+mld-IR indicate w 1118 ; UAS-dicer2/+; phm-GAL4#22/+ and w 1118 ; UAS-dicer2/UAS-mld-IR; phm-GAL4#22/+, respectively. RNA samples were collected 36 hours after egg laying. Bars...

The temporal expression profiles of ouib expression and ecdysteroid levels during the third instar larval development. ouib expression and ecdysteroid levels in w 1118 during the 3rd instar stage measured by qRT-PCR (N = 3) and ELISA (N = 4). The blue line indicates the relative expression level of ouib, normalized to the level of 0–6 hours after...

The evolutionary conservation of sequences similar to Ouib-response element in putative spok enhancer/promoter regions of 12 Drosophilidae species. EMBOSS Matcher [54] was used to search for sequences similar to the D. melanogaster Ouib response element (15 bp) within the 1 kb regions upstream of the translation initiation site of the spok loci fro...

Significance Metamorphosis is an important biological process by which animals alter their body structures to become sexually mature adults. We discovered that tyramine signaling through the β3-octopamine receptor plays an essential role in producing the steroid hormone ecdysone, which is critical for metamorphosis. Based on our observations, we pr...

The temporal transition of development is flexibly coordinated in the context of the nutrient environment, and this coordination is essential for organisms to increase their survival fitness and reproductive success. Steroid hormone, a key player of the juvenile-to-adult transition, is biosynthesized in a nutrient-dependent manner; however, the und...

Egg chambers from starved Drosophila females contain large aggregates of processing (P) bodies and cortically enriched microtubules. As this response to starvation is rapidly reversed upon re-feeding females or culturing egg chambers with exogenous bovine insulin, we examined the role of endogenous insulin signaling in mediating the starvation resp...

Steroid hormones are responsible for the coordinated regulation of many aspects of biological processes in multicellular organisms. Since the last century, many studies have identified and characterized steroidogenic enzymes in vertebrates, including mammals. However, much less is known about invertebrate steroidogenic enzymes. In the last 15 years...

The insect steroid hormone ecdysteroid plays pivotal roles in the temporal coordination of development, represented by molting and metamorphosis. During the larval stages, ecdysteroid is biosynthesized from dietary cholesterol by several ecdysteroidogenic enzymes in the specialized endocrine organ called the prothoracic gland (PG). As ecdysteroid b...

Ring canals connecting Drosophila germline, follicle and imaginal disc cells provide direct contact of cytoplasm between cells. To date, little is known about the formation, structure, or function of the somatic ring canals present in follicle and imaginal disc cells. Here, we show by confocal and electron microscopy that Pavarotti kinesin-like pro...

The maturation of animal oocytes is highly sensitive to nutrient availability. During Drosophila oogenesis, a prominent metabolic checkpoint occurs at the onset of yolk uptake (vitellogenesis): under nutrient stress, egg chambers degenerate by apoptosis. To investigate additional responses to nutrient deprivation, we studied the intercellular trans...

Steroid hormones play essential roles in a wide variety of biological processes in multicellular organisms. The principal steroid hormones in nematodes and arthropods are dafachronic acids and ecdysteroids, respectively, both of which are synthesized from cholesterol as an indispensable precursor. The first critical catalytic step in the biosynthes...

Cholesterol has long been recognized for its versatile roles in influencing the biophysical properties of cell membranes and for serving as a precursor of steroid hormones. While many aspects of cholesterol biosynthesis are well understood, little is currently known about the molecular mechanisms of cholesterol metabolism and homeostasis. Recently,...

How global organ asymmetry and individual cell polarity are connected to each other is a central question in studying planar cell polarity (PCP). In the Drosophila wing, which develops PCP along its proximal-distal (P-D) axis, we previously proposed that the core PCP mediator Frizzled redistributes distally in a microtubule (MT)-dependent manner. H...

In insects, the precise timing of molting and metamorphosis is strictly guided by a principal steroid hormone, ecdysone. Among the multiple conversion steps for synthesizing ecdysone from dietary cholesterol, the conversion of 7-dehydrocholesterol to 5beta-ketodiol, the so-called 'Black Box', is thought to be the important rate-limiting step. Altho...

Cells in a variety of developmental contexts sense extracellular cues that are given locally on their surfaces, and subsequently amplify the initial signal to achieve cell polarization. Drosophila wing cells acquire planar polarity along the proximal-distal (P-D) axis, in which the amplification of the presumptive cue involves assembly of a multipr...

In many organs, epithelial cells are polarized not only along the apicobasal axis, but also along a second axis within a plane. Acquisition of the latter polarity, known as planar cell polarity (PCP) or tissue polarity, is crucial for specialized cellular functions. Genetic programming of PCP has been most thoroughly studied in Drosophila, which ha...

The Drosophila wing provides an appropriate model system for studying genetic programming of planar cell polarity (PCP) [1-4]. Each wing cell respects the proximodistal (PD) axis; i.e., it localizes an assembly of actin bundles to its distalmost vertex and produces a single prehair. This PD polarization requires the redistribution of Flamingo (Fmi)...

We identified a seven-pass transmembrane receptor of the cadherin superfamily, designated Flamingo (Fmi), localized at cell-cell boundaries in the Drosophila wing. In the absence of Fmi, planar polarity was distorted. Before morphological polarization of wing cells along the proximal-distal (P-D) axis, Fmi was redistributed predominantly to proxima...