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Current Biology : CB Feb 2024Germ cells are essential to sexual reproduction. Across the animal kingdom, extracellular signaling isoprenoids, such as retinoic acids (RAs) in vertebrates and juvenile...
Germ cells are essential to sexual reproduction. Across the animal kingdom, extracellular signaling isoprenoids, such as retinoic acids (RAs) in vertebrates and juvenile hormones (JHs) in invertebrates, facilitate multiple processes in reproduction. Here we investigated the role of these potent signaling molecules in embryonic germ cell development, using JHs in Drosophila melanogaster as a model system. In contrast to their established endocrine roles during larval and adult germline development, we found that JH signaling acts locally during embryonic development. Using an in vivo biosensor, we observed active JH signaling first within and near primordial germ cells (PGCs) as they migrate to the developing gonad. Through in vivo and in vitro assays, we determined that JHs are both necessary and sufficient for PGC migration. Analysis into the mechanisms of this newly uncovered paracrine JH function revealed that PGC migration was compromised when JHs were decreased or increased, suggesting that specific titers or spatiotemporal JH dynamics are required for robust PGC colonization of the gonad. Compromised PGC migration can impair fertility and cause germ cell tumors in many species, including humans. In mammals, retinoids have many roles in development and reproduction. We found that like JHs in Drosophila, RA was sufficient to impact mouse PGC migration in vitro. Together, our study reveals a previously unanticipated role of isoprenoids as local effectors of pre-gonadal PGC development and suggests a broadly shared mechanism in PGC migration.
Topics: Humans; Mice; Animals; Drosophila melanogaster; Juvenile Hormones; Germ Cells; Drosophila; Gonads; Terpenes; Cell Movement; Mammals
PubMed: 38215744
DOI: 10.1016/j.cub.2023.12.033 -
PLoS Genetics Sep 2023TAIMAN (TAI), the only insect ortholog of mammalian Steroid Receptor Coactivators (SRCs), is a critical modulator of ecdysone and juvenile hormone (JH) signaling...
TAIMAN (TAI), the only insect ortholog of mammalian Steroid Receptor Coactivators (SRCs), is a critical modulator of ecdysone and juvenile hormone (JH) signaling pathways, which govern insect development and reproduction. The modulatory effect is mediated by JH-dependent TAI's heterodimerization with JH receptor Methoprene-tolerant and association with the Ecdysone Receptor complex. Insect hormones regulate insect physiology and development in concert with abiotic cues, such as photo- and thermoperiod. Here we tested the effects of JH and ecdysone signaling on the circadian clock by a combination of microsurgical operations, application of hormones and hormone mimics, and gene knockdowns in the linden bug Pyrrhocoris apterus males. Silencing taiman by each of three non-overlapping double-strand RNA fragments dramatically slowed the free-running period (FRP) to 27-29 hours, contrasting to 24 hours in controls. To further corroborate TAIMAN's clock modulatory function in the insect circadian clock, we performed taiman knockdown in the cockroach Blattella germanica. Although Blattella and Pyrrhocoris lineages separated ~380 mya, B. germanica taiman silencing slowed the FRP by more than 2 hours, suggesting a conserved TAI clock function in (at least) some insect groups. Interestingly, the pace of the linden bug circadian clock was neither changed by blocking JH and ecdysone synthesis, by application of the hormones or their mimics nor by the knockdown of corresponding hormone receptors. Our results promote TAI as a new circadian clock modulator, a role described for the first time in insects. We speculate that TAI participation in the clock is congruent with the mammalian SRC-2 role in orchestrating metabolism and circadian rhythms, and that TAI/SRCs might be conserved components of the circadian clock in animals.
Topics: Animals; Male; Circadian Clocks; Ecdysone; Insecta; Circadian Rhythm; Cell Membrane; Juvenile Hormones; Mammals
PubMed: 37683015
DOI: 10.1371/journal.pgen.1010924 -
International Journal of Molecular... May 2022The sesquiterpenoid hormone juvenile hormone (JH) controls development, reproduction, and metamorphosis in insects, and has long been thought to be confined to the...
The sesquiterpenoid hormone juvenile hormone (JH) controls development, reproduction, and metamorphosis in insects, and has long been thought to be confined to the Insecta. While it remains true that juvenile hormone is specifically synthesized in insects, other types or forms of sesquiterpenoids have also been discovered in distantly related animals, such as the jellyfish. Here, we combine the latest literature and annotate the sesquiterpenoid biosynthetic pathway genes in different animal genomes. We hypothesize that the sesquiterpenoid hormonal system is an ancestral system established in an animal ancestor and remains widespread in many animals. Different animal lineages have adapted different enzymatic routes from a common pathway, with cnidarians producing farnesoic acid (FA); non-insect protostomes and non-vertebrate deuterostomes such as cephalochordate and echinoderm synthesizing FA and methyl farnesoate (MF); and insects producing FA, MF, and JH. Our hypothesis revolutionizes the current view on the sesquiterpenoids in the metazoans, and forms a foundation for a re-investigation of the roles of this important and yet neglected type of hormone in different animals.
Topics: Animals; Biosynthetic Pathways; Insecta; Juvenile Hormones; Metamorphosis, Biological; Sesquiterpenes
PubMed: 35682678
DOI: 10.3390/ijms23115998 -
Current Opinion in Cell Biology Aug 2012The Notch signaling pathway controls patterning and cell fate decisions during development in metazoans, and is associated with human diseases such as cerebral autosomal... (Review)
Review
The Notch signaling pathway controls patterning and cell fate decisions during development in metazoans, and is associated with human diseases such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and certain cancers. Studies over the last several years have revealed sophisticated regulation of both the membrane-bound Notch receptor and its ligands by vesicle trafficking. This is perhaps most evident in neural progenitor cells in Drosophila, which divide asymmetrically to segregate Numb, an endocytic adaptor protein that acts as a Notch pathway inhibitor, to one daughter cell. Here, we discuss recent findings addressing how receptor and ligand trafficking to specific membrane compartments control activation of the Notch pathway in asymmetrically dividing cells and other tissues.
Topics: Animals; Asymmetric Cell Division; Drosophila Proteins; Drosophila melanogaster; Endocytosis; Humans; Juvenile Hormones; Ligands; Neural Stem Cells; Protein Transport; Receptors, Notch; Signal Transduction
PubMed: 22818956
DOI: 10.1016/j.ceb.2012.06.006 -
Biological & Pharmaceutical Bulletin 2012In insects molting and metamorphosis are primarily under the control of two insect hormones, ecdysone and juvenile hormone (JH). Physiological and biochemical studies of... (Review)
Review
In insects molting and metamorphosis are primarily under the control of two insect hormones, ecdysone and juvenile hormone (JH). Physiological and biochemical studies of insect hormone metabolic pathways suggested the involvement of P450 (CYP) enzymes in the pathways, but molecular details of the enzymes were unclear. In recent years, the genome information and studies using molecular biology and genetics have allowed us to understand enzymes in the ecdysteroid and JH metabolic pathways. Genome sequencing has been accomplished in several insect species, and has shown the presence of 36-180 CYP enzymes. To date, six and one CYP enzymes have been revealed in the biosynthesis and inactivation pathways of 20-hydroxyecdysone (20E), respectively. In the 20E biosynthetic pathway, correlation among the enzymes, substrates and metabolites is elucidated in the late steps, but the enzyme(s) and intermediates in the early steps have not been fully understood and are referred to as the 'Black Box'. The gene expression of some CYP enzymes in the 20E biosynthesis is modulated by neuropeptides and JH. Furthermore, involvement of a CYP enzyme is found in both JH biosynthesis and inactivation pathways. Thus, recent studies have shown the importance of CYP enzymes in insect hormone metabolisms.
Topics: Animals; Cytochrome P-450 Enzyme System; Ecdysteroids; Insect Proteins; Juvenile Hormones
PubMed: 22687472
DOI: 10.1248/bpb.35.838 -
EMBO Reports Mar 2007
Review
Topics: Animals; Cell Adhesion Molecules; Cell Cycle Proteins; Cell Polarity; Drosophila Proteins; Intracellular Signaling Peptides and Proteins; Juvenile Hormones; Membrane Proteins; Multiprotein Complexes; Protein Kinase C; Tight Junctions
PubMed: 17330067
DOI: 10.1038/sj.embor.7400928 -
Hormone-related genes heterochronically and modularly regulate neotenic differentiation in termites.Developmental Biology May 2022Caste development in social insects requires the coordination of molting and metamorphosis during postembryonic development. In termites, i.e., hemimetabolous eusocial...
Caste development in social insects requires the coordination of molting and metamorphosis during postembryonic development. In termites, i.e., hemimetabolous eusocial insects, caste fate is determined during postembryonic development. However, it is not fully understood how the mechanisms of molting/metamorphosis are regulated in the course of differentiation between reproductive and sterile castes. In termites, only reproductives derived from alates are imagos and other sterile castes (including developmentally-terminal soldier caste) are basically juveniles or nymphs. Furthermore, supplementary reproductives that appear when the original queens and kings die or become senescent, exhibit larval features such as winglessness, and are called neotenics. Therefore, the question of whether neotenics are larvae or imagos is still under debate. In this study, by inducing female neotenic differentiation in a damp-wood termite Hodotermopsis sjostedti, morphological investigations together with juvenile hormone (JH) quantification and expression/functional analyses of genes responsible for molting and/or metamorphosis were carried out. JH titer and expression of one of the downstream genes (Kr-h1) were shown to be temporarily lowered, but increased just prior to the molt into neotenics, while consistently lowered in imaginal molt (i.e., alate differentiation). In contrast, ecdysone-related genes (EcR and E93) were upregulated at both neotenic and alate differentiation, suggesting that the heterochronic actions of ecdysone and JH lead the neotenic differentiation. Moreover, expression analyses, supported by reverse genetic experiments, showed that EcR and E93 were specifically upregulated in genital sternites (EcR and E93) and ovaries (E93) and required for the development of imaginal characters. These results suggest that the resultant mosaic phenotype of female neotenics is due to modular responses of different body parts to hormonal actions.
Topics: Animals; Ecdysone; Female; Isoptera; Juvenile Hormones; Molting; Sex Differentiation
PubMed: 35248548
DOI: 10.1016/j.ydbio.2022.02.012 -
PLoS Genetics Aug 2022The decision to engage in courtship depends on external cues from potential mates and internal cues related to maturation, health, and experience. Hormones allow for...
The decision to engage in courtship depends on external cues from potential mates and internal cues related to maturation, health, and experience. Hormones allow for coordinated conveyance of such information to peripheral tissues. Here, we show Ecdysis-Triggering Hormone (ETH) is critical for courtship inhibition after completion of copulation in Drosophila melanogaster. ETH deficiency relieves post-copulation courtship inhibition (PCCI) and increases male-male courtship. ETH appears to modulate perception and attractiveness of potential mates by direct action on primary chemosensory neurons. Knockdown of ETH receptor (ETHR) expression in GR32A-expressing neurons leads to reduced ligand sensitivity and elevated male-male courtship. We find OR67D also is critical for normal levels of PCCI after mating. ETHR knockdown in OR67D-expressing neurons or GR32A-expressing neurons relieves PCCI. Finally, ETHR silencing in the corpus allatum (CA), the sole source of juvenile hormone, also relieves PCCI; treatment with the juvenile hormone analog methoprene partially restores normal post-mating behavior. We find that ETH, a stress-sensitive reproductive hormone, appears to coordinate multiple sensory modalities to guide Drosophila male courtship behaviors, especially after mating.
Topics: Animals; Courtship; Drosophila; Drosophila Proteins; Drosophila melanogaster; Juvenile Hormones; Male; Neurons; Sexual Behavior, Animal
PubMed: 35998183
DOI: 10.1371/journal.pgen.1010357 -
International Journal of Molecular... Nov 2022Insect development requires genes to be expressed in strict spatiotemporal order. The dynamic regulation of genes involved in insect development is partly orchestrated...
Insect development requires genes to be expressed in strict spatiotemporal order. The dynamic regulation of genes involved in insect development is partly orchestrated by the histone acetylation-deacetylation via histone acetyltransferases (HATs) and histone deacetylases (HDACs). Although histone deacetylase 3 (HDAC3) is required for mice during early embryonic development, its functions in () and its potential to be used as a target of insecticides remain unclear. We treated with HDAC3 siRNA and RGFP966, a specific inhibitor, examining how the HDAC3 loss-of-function affects growth and development. HDAC3 siRNA and RGFP966 treatment increased mortality at each growth stage and altered metamorphosis, hampering pupation and causing abnormal wing development, reduced egg production, and reduced hatching rate. We believe that the misregulation of key hormone-related genes leads to abnormal pupa development in HDAC3 knockout insects. RNA-seq analysis identified 2788 differentially expressed genes (≥two-fold change; ≤ 0.05) between siHDAC3- and siNC-treated larvae. Krüppel homolog 1 (Kr-h1), was differentially expressed in HDAC3 knockdown larvae. Pathway-enrichment analysis revealed the significant enrichment of genes involved in the Hippo, MAPK, and Wnt signaling pathways following HDAC3 knockdown. Histone H3K9 acetylation was increased in after siHDAC3 treatment. In conclusion, HDAC3 knockdown dysregulated juvenile hormone (JH)-related and apoptosis-related genes in The results showed that the HDAC3 gene is a potential target for fighting .
Topics: Mice; Animals; Juvenile Hormones; Histones; Histone Deacetylases; Moths; Apoptosis; Larva
PubMed: 36499148
DOI: 10.3390/ijms232314820 -
Biomolecules Jul 2022Juvenile hormone epoxide hydrolase (JHEH) plays an important role in the metabolism of JH III in insects. To study the control of JHEH in female , JHEH 1, 2 and 3 cDNAs...
Juvenile hormone epoxide hydrolase (JHEH) plays an important role in the metabolism of JH III in insects. To study the control of JHEH in female , JHEH 1, 2 and 3 cDNAs were cloned and sequenced. Northern blot analyses showed that the three transcripts are expressed in the head thorax, the gut, the ovaries and the fat body of females. Molecular modeling shows that the enzyme is a homodimer that binds juvenile hormone III acid (JH IIIA) at the catalytic groove better than JH III. Analyses of the three JHEH promoters and expressing short promoter sequences behind a reporter gene (Z) in cell culture identified a JHEH 3 promoter sequence (626 bp) that is 10- and 25-fold more active than the most active promoter sequences of JHEH 2 and JHEH 1, respectively. A transcription factor (TF) Sp1 that is involved in the activation of JHEH 3 promoter sequence was identified. Knocking down Sp1 using dsRNA inhibited the transcriptional activity of this promoter in transfected cells and JH III and 20HE downregulated the JHEH 3 promoter. On the other hand, JH IIIA and farnesoic acid did not affect the promoter, indicating that JH IIIA is JHEH's preferred substrate. A transgenic expressing a highly activated JHEH 3 promoter behind a Z reporter gene showed promoter transcriptional activity in many tissues.
Topics: Animals; Cloning, Molecular; Drosophila melanogaster; Epoxide Hydrolases; Female; Juvenile Hormones
PubMed: 35883546
DOI: 10.3390/biom12070991