scholarly journals Regulatory mechanisms underlying the specification of the pupal-homologous stage in a hemimetabolous insect

2019 ◽  
Vol 374 (1783) ◽  
pp. 20190225 ◽  
Author(s):  
Yoshiyasu Ishimaru ◽  
Sayuri Tomonari ◽  
Takahito Watanabe ◽  
Sumihare Noji ◽  
Taro Mito
Keyword(s):  
Genetic Interaction ◽  
Pupal Stage ◽  
Regulatory Mechanisms ◽  
Stage Versus ◽  
Nymphal Instar ◽  
Gryllus Bimaculatus ◽  
Theme Issue ◽  
Evolutionarily Conserved ◽  
Hemimetabolous Insect ◽  
Complete Metamorphosis

Juvenile hormones and the genetic interaction between the transcription factors Krüppel homologue 1 ( Kr-h1 ) and Broad ( Br ) regulate the transformation of insects from immature to adult forms in both types of metamorphosis (holometaboly with a pupal stage versus hemimetaboly with no pupal stage); however, knowledge about the exact instar in which this occurs is limited. Using the hemimetabolous cricket Gryllus bimaculatus ( Gb ), we demonstrate that a genetic interaction occurs among Gb ′ Kr-h1 , Gb ′ Br and the adult-specifier transcription factor Gb ′ E93 from the sixth to final (eighth) nymphal instar. Gb ′ Kr-h1 and Gb ′ Br mRNAs were strongly expressed in the abdominal tissues of sixth instar nymphs, with precocious adult moults being induced by Gb ′ Kr-h1 or Gb ′ Br knockdown in the sixth instar. The depletion of Gb ′ Kr-h1 or Gb ′ Br upregulates Gb ′ E93 in the sixth instar. By contrast, Gb ′ E93 knockdown at the sixth instar prevents nymphs transitioning to adults, instead producing supernumerary nymphs. Gb ′ E93 also represses Gb ′ Kr-h1 and Gb ′ Br expression in the penultimate nymphal instar, demonstrating its important role in adult differentiation. Our results suggest that the regulatory mechanisms underlying the pupal transition in holometabolous insects are evolutionarily conserved in hemimetabolous G . bimaculatus , with the penultimate and final nymphal periods being equivalent to the pupal stage. This article is part of the theme issue ‘The evolution of complete metamorphosis’.

scholarly journals Immune gene regulation in the gut during metamorphosis in a holo- versus a hemimetabolous insect

2019 ◽  
Vol 374 (1783) ◽  
pp. 20190073 ◽  
Author(s):  
Paul R. Johnston ◽  
Véronique Paris ◽  
Jens Rolff
Keyword(s):  
Galleria Mellonella ◽  
Immune Gene ◽  
Gryllus Bimaculatus ◽  
Theme Issue ◽  
Immune Effector ◽  
Rapid Induction ◽  
Effector Genes ◽  
Hemimetabolous Insect ◽  
Insect Gut ◽  
Complete Metamorphosis

During metamorphosis, holometabolous insects completely replace the larval gut and must control the microbiota to avoid septicaemia. Rapid induction of bactericidal activity in the insect gut at the onset of pupation has been described in numerous orders of the Holometabola and is best-studied in the Lepidoptera where it is under control of the 20-hydroxyecdysone (20E) moulting pathway. Here, using RNAseq, we compare the expression of immune effector genes in the gut during metamorphosis in a holometabolous ( Galleria mellonella ) and a hemimetabolous insect ( Gryllus bimaculatus ). We find that in G. mellonella , the expression of numerous immune effectors and the transcription factor GmEts are upregulated, with peak expression of three antimicrobial peptides (AMPs) and a lysozyme coinciding with delamination of the larval gut. By contrast, no such upregulation was detectable in the hemimetabolous Gr. bimaculatus . These findings support the idea that the upregulation of immune effectors at the onset of complete metamorphosis is an adaptive response, which controls the microbiota during gut replacement. This article is part of the theme issue ‘The evolution of complete metamorphosis’.

scholarly journals Antipredator strategies of pupae: how to avoid predation in an immobile life stage?

2019 ◽  
Vol 374 (1783) ◽  
pp. 20190069 ◽  
Author(s):  
Carita Lindstedt ◽  
Liam Murphy ◽  
Johanna Mappes
Keyword(s):  
Life Stage ◽  
Pupal Stage ◽  
Future Research ◽  
Theme Issue ◽  
Antipredator Strategies ◽  
Individual Fitness ◽  
Cryptic Coloration ◽  
Wide Range ◽  
Common Strategy ◽  
Complete Metamorphosis

Antipredator strategies of the pupal stage in insects have received little attention in comparison to larval or adult stages. This is despite the fact that predation risk can be high during the pupal stage, making it a critical stage for subsequent fitness. The immobile pupae are not, however, defenceless; a wide range of antipredator strategies have evolved against invertebrate and vertebrate predators. The most common strategy seems to be ‘avoiding encounters with predators' by actively hiding in vegetation and soil or via cryptic coloration and masquerade. Pupae have also evolved behavioural and secondary defences such as defensive toxins, physical defences or deimatic movements and sounds. Interestingly, warning coloration used to advertise unprofitability has evolved very rarely, even though the pupal stage often contains defensive toxins in chemically defended species. In some species, pupae gain protection from conspecifics or mimic chemical and auditory signals and thereby manipulate other species to protect them. Our literature survey highlights the importance of studying selection pressures across an individual's life stages to predict how ontogenetic variation in selective environments shapes individual fitness and population dynamics in insects. Finally, we also suggest interesting avenues for future research to pursue. This article is part of the theme issue ‘The evolution of complete metamorphosis’.

scholarly journals Complete metamorphosis of insects

2019 ◽  
Vol 374 (1783) ◽  
pp. 20190063 ◽  
Author(s):  
Jens Rolff ◽  
Paul R. Johnston ◽  
Stuart Reynolds
Keyword(s):  
Adult Stage ◽  
Pupal Stage ◽  
Life Stages ◽  
Micro Ct ◽  
Larval Form ◽  
Theme Issue ◽  
The Cost ◽  
Ephemeral Resources ◽  
Complete Metamorphosis

The majority of described hexapod species are holometabolous insects, undergoing an extreme form of metamorphosis with an intercalated pupal stage between the larva and adult, in which organs and tissues are extensively remodelled and in some cases completely rebuilt. Here, we review how and why this developmental strategy has evolved. While there are many theories explaining the evolution of metamorphosis, many of which fit under the hypothesis of decoupling of life stages, there are few clear adaptive hypotheses on why complete metamorphosis evolved. We propose that the main adaptive benefit of complete metamorphosis is decoupling between growth and differentiation. This facilitates the exploitation of ephemeral resources and enhances the probability of the metamorphic transition escaping developmental size thresholds. The evolution of complete metamorphosis comes at the cost of exposure to predators, parasites and pathogens during pupal life and requires specific adaptations of the immune system at this time. Moreover, metamorphosis poses a challenge for the maintenance of symbionts and the gut microbiota, although it may also offer the benefit of allowing an extensive change in microbiota between the larval and adult stages. The regulation of metamorphosis by two main players, ecdysone and juvenile hormone, and the related signalling cascades are now relatively well understood. The mechanics of metamorphosis have recently been studied in detail because of the advent of micro-CT and research into the role of cell death in remodelling tissues and organs. We support the argument that the adult stage must necessarily have preceded the larval form of the insect. We do not resolve the still contentious question of whether the larva of insects in general originated through the modification of existing preadult forms or through heterochrony as a modified embryonic stage (pronymph), nor whether the holometabolous pupa arose as a modified hemimetabolous final stage larva. This article is part of the theme issue ‘The evolution of complete metamorphosis’.

scholarly journals Emerging multifaceted roles of BAP1 complexes in biological processes

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Aileen Patricia Szczepanski ◽  
Lu Wang
Keyword(s):  
Transcriptional Repression ◽  
Target Genes ◽  
Regulatory Mechanisms ◽  
Biological Processes ◽  
Multiprotein Complex ◽  
Downstream Target ◽  
Evolutionarily Conserved ◽  
Complex Forms ◽  
Polycomb Repressive Complex 1

AbstractHistone H2AK119 mono-ubiquitination (H2AK119Ub) is a relatively abundant histone modification, mainly catalyzed by the Polycomb Repressive Complex 1 (PRC1) to regulate Polycomb-mediated transcriptional repression of downstream target genes. Consequently, H2AK119Ub can also be dynamically reversed by the BAP1 complex, an evolutionarily conserved multiprotein complex that functions as a general transcriptional activator. In previous studies, it has been reported that the BAP1 complex consists of important biological roles in development, metabolism, and cancer. However, identifying the BAP1 complex’s regulatory mechanisms remains to be elucidated due to its various complex forms and its ability to target non-histone substrates. In this review, we will summarize recent findings that have contributed to the diverse functional role of the BAP1 complex and further discuss the potential in targeting BAP1 for therapeutic use.

scholarly journals Cleavage activates Dispatched for Sonic Hedgehog ligand release

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Daniel P Stewart ◽  
Suresh Marada ◽  
William J Bodeen ◽  
Ashley Truong ◽  
Sadie Miki Sakurada ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Membrane Trafficking ◽  
Developmental Disorders ◽  
Transmembrane Protein ◽  
Regulatory Mechanisms ◽  
Extracellular Loop ◽  
Site Mutation ◽  
Evolutionarily Conserved ◽  
Processing Site

Hedgehog ligands activate an evolutionarily conserved signaling pathway that provides instructional cues during tissue morphogenesis, and when corrupted, contributes to developmental disorders and cancer. The transmembrane protein Dispatched is an essential component of the machinery that deploys Hedgehog family ligands from producing cells, and is absolutely required for signaling to long-range targets. Despite this crucial role, regulatory mechanisms controlling Dispatched activity remain largely undefined. Herein, we reveal vertebrate Dispatched is activated by proprotein convertase-mediated cleavage at a conserved processing site in its first extracellular loop. Dispatched processing occurs at the cell surface to instruct its membrane re-localization in polarized epithelial cells. Cleavage site mutation alters Dispatched membrane trafficking and reduces ligand release, leading to compromised pathway activity in vivo. As such, convertase-mediated cleavage is required for Dispatched maturation and functional competency in Hedgehog ligand-producing cells.

scholarly journals SUMO modification in apoptosis

2020 ◽  
Vol 52 (1) ◽  
pp. 1-10
Author(s):  
Peiyao Li ◽  
Huiru Jing ◽  
Yanzhe Wang ◽  
Lei Yuan ◽  
Hui Xiao ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Neurodegenerative Diseases ◽  
Growth And Development ◽  
Recent Progress ◽  
Biological Process ◽  
Regulatory Mechanisms ◽  
Apoptotic Cells ◽  
Post Translational Modification ◽  
Sumo Modification ◽  
Evolutionarily Conserved

AbstractApoptosis and clearance of dead cells is highly evolutionarily conserved from nematode to humans, which is crucial to the growth and development of multicellular organism. Fail to remove apoptotic cells often lead to homeostasis imbalance, fatal autoimmune diseases, and neurodegenerative diseases. Small ubiquitin-related modifiers (SUMOs) modification is a post-translational modification of ubiquitin proteins mediated by the sentrin-specific proteases (SENPs) family. SUMO modification is widely involved in many cellular biological process, and abnormal SUMO modification is also closely related to many major human diseases. Recent researches have revealed that SUMO modification event occurs during apoptosis and clearance of apoptotic cells, and plays an important role in the regulation of apoptotic signaling pathways. This review summarizes some recent progress in the revelation of regulatory mechanisms of these pathways and provides some potential researching hotpots of the SUMO modification regulation to apoptosis.

scholarly journals Evolutionarily conserved genetic interactions between nphp-4 and bbs-5 mutations exacerbate ciliopathy phenotypes

Genetics ◽  
2021 ◽  
Author(s):  
Melissa R Bentley-Ford ◽  
Melissa LaBonty ◽  
Holly R Thomas ◽  
Courtney J Haycraft ◽  
Mikyla Scott ◽  
...  
Keyword(s):  
Double Mutant ◽  
Primary Cilia ◽  
Protein Transport ◽  
Genetic Interaction ◽  
Synergistic Effects ◽  
Phenotypic Variability ◽  
Protein Composition ◽  
Mutant Mice ◽  
Mouse Mutants ◽  
Evolutionarily Conserved

Abstract Primary cilia are sensory and signaling hubs with a protein composition that is distinct from the rest of the cell due to the barrier function of the transition zone (TZ) at the base of the cilium. Protein transport across the TZ is mediated in part by the BBSome, and mutations disrupting TZ and BBSome proteins cause human ciliopathy syndromes. Ciliopathies have phenotypic variability even among patients with identical genetic variants, suggesting a role for modifier loci. To identify potential ciliopathy modifiers, we performed a mutagenesis screen on nphp-4 mutant Caenorhabditis elegans and uncovered a novel allele of bbs-5. Nphp-4;bbs-5 double mutant worms have phenotypes not observed in either individual mutant strain. To test whether this genetic interaction is conserved, we also analyzed zebrafish and mouse mutants. While Nphp4 mutant zebrafish appeared overtly normal, Bbs5 mutants exhibited scoliosis. When combined, Nphp4;Bbs5 double mutant zebrafish did not exhibit synergistic effects, but the lack of a phenotype in Nphp4 mutants makes interpreting these data difficult. In contrast, Nphp4;Bbs5 double mutant mice were not viable and there were fewer mice than expected carrying three mutant alleles. In addition, postnatal loss of Bbs5 in mice using a conditional allele compromised survival when combined with an Nphp4 allele. As cilia are still formed in the double mutant mice, the exacerbated phenotype is likely a consequence of disrupted ciliary signaling. Collectively, these data support an evolutionarily conserved genetic interaction between Bbs5 and Nphp4 alleles that may contribute to the variability in ciliopathy phenotypes.

scholarly journals The Evolutionary Conserved Transmembrane BAX Inhibitor Motif (TMBIM) Containing Protein Family is Essential for the Development and Survival of Drosophila Melanogaster

2020 ◽  
Author(s):  
Li Zhang ◽  
Sebastian Buhr ◽  
Vibha Prasad ◽  
Aaron Voigt ◽  
Axel Methner
Keyword(s):  
Drosophila Melanogaster ◽  
Genetic Interaction ◽  
Family Members ◽  
Protein Family ◽  
Tissue Specific ◽  
Similar Expression Pattern ◽  
Evolutionarily Conserved ◽  
Extended Lifespan ◽  
Ph Dependent ◽  
Er Calcium

Abstract The Transmembrane BAX Inhibitor Motif (TMBIM) protein family consists of six evolutionarily conserved hydrophobic proteins that affect programmed cell death and the regulation of intracellular calcium levels. The bacterial orthologue BsYetJ is a pH-dependent calcium channel. We here identified six TMBIM family members in Drosophila melanogaster and studied the effect of their RNAi-mediated knockdown using ubiquitous and tissue-specific drivers. Mammalian TMBIM6 and TMBIM5 have obvious orthologs while this is more dubious for the other family members. Ubiquitous knockdown of family members dmTMBIM1,4,5, and 6 caused failed eclosing and tissue-specific knockdown resulted in a dramatically decreased lifespan. On the contrary, knockdown of dmTMBIM3, surprisingly, extended lifespan. Only knockdown of dmTMBIM6 increased the ER calcium levels of Pdf neurons. Neural knockdown of dmTMBIM2,3, and 4 increased ER stress, as indicated by increased Xbp1 splicing. Interestingly, TMBIM1 and TMBIM6 have a very similar expression pattern and their knockdown phenocopied each other. Also, knockdown of TMBIM1 resulted in upregulation of TMBIM6 and vice versa further suggesting a genetic interaction between these two genes. Our data demonstrate that most TMBIM proteins are essential for fly development and survival but, despite their shared protein structure, affect cell survival through different mechanisms.

scholarly journals Targeting Notch Trafficking and Processing in Cancers

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2212 ◽  
Author(s):  
Luca Pagliaro ◽  
Claudia Sorrentino ◽  
Giovanni Roti
Keyword(s):  
Endoplasmic Reticulum ◽  
Notch Signaling ◽  
Functional Relationship ◽  
Regulatory Elements ◽  
Ion Concentration ◽  
Regulatory Mechanisms ◽  
Subcellular Compartments ◽  
Evolutionarily Conserved ◽  
Potential Alternative

The Notch family comprises a group of four ligand-dependent receptors that control evolutionarily conserved developmental and homeostatic processes and transmit signals to the microenvironment. NOTCH undergoes remodeling, maturation, and trafficking in a series of post-translational events, including glycosylation, ubiquitination, and endocytosis. The regulatory modifications occurring in the endoplasmic reticulum/Golgi precede the intramembrane γ-secretase proteolysis and the transfer of active NOTCH to the nucleus. Hence, NOTCH proteins coexist in different subcellular compartments and undergo continuous relocation. Various factors, including ion concentration, enzymatic activity, and co-regulatory elements control Notch trafficking. Interfering with these regulatory mechanisms represents an innovative therapeutic way to bar oncogenic Notch signaling. In this review, we briefly summarize the role of Notch signaling in cancer and describe the protein modifications required for NOTCH to relocate across different subcellular compartments. We focus on the functional relationship between these modifications and the corresponding therapeutic options, and our findings could support the development of trafficking modulators as a potential alternative to the well-known γ-secretase inhibitors.

scholarly journals A framework for exhaustive modelling of genetic interaction patterns using Petri nets

2019 ◽  
Vol 36 (7) ◽  
pp. 2142-2149
Author(s):  
Annika Jacobsen ◽  
Olga Ivanova ◽  
Saman Amini ◽  
Jaap Heringa ◽  
Patrick Kemmeren ◽  
...  
Keyword(s):  
Petri Nets ◽  
Drug Response ◽  
Genetic Interaction ◽  
Regulatory Mechanisms ◽  
Supplementary Information ◽  
Biological Processes ◽  
Interaction Patterns ◽  
Supplementary Data ◽  
Gene Pairs ◽  
Computational Analyses

Abstract Motivation Genetic interaction (GI) patterns are characterized by the phenotypes of interacting single and double mutated gene pairs. Uncovering the regulatory mechanisms of GIs would provide a better understanding of their role in biological processes, diseases and drug response. Computational analyses can provide insights into the underpinning mechanisms of GIs. Results In this study, we present a framework for exhaustive modelling of GI patterns using Petri nets (PN). Four-node models were defined and generated on three levels with restrictions, to enable an exhaustive approach. Simulations suggest ∼5 million models of GIs. Generalizing these we propose putative mechanisms for the GI patterns, inversion and suppression. We demonstrate that exhaustive PN modelling enables reasoning about mechanisms of GIs when only the phenotypes of gene pairs are known. The framework can be applied to other GI or genetic regulatory datasets. Availability and implementation The framework is available at http://www.ibi.vu.nl/programs/ExhMod. Supplementary information Supplementary data are available at Bioinformatics online.

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