scholarly journals Changes in splicing and neuromodulatory gene expression programs in sensory neurons with pheromone signaling and social experience

2021 ◽  
Author(s):  
Pelin C Volkan ◽  
Bryson Deanhardt ◽  
Qichen Duan ◽  
Chengcheng Du ◽  
Charles Soeder ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Molecular Mechanisms ◽  
Social Experience ◽  
Rna Seq ◽  
Male Courtship ◽  
Wild Type ◽  
Pheromone Signaling ◽  
Courtship Behaviors ◽  
Necessary And Sufficient ◽  
Splicing Patterns

Social experience and pheromone signaling in ORNs affect pheromone responses and male courtship behaviors in Drosophila, however, the molecular mechanisms underlying this circuit-level neuromodulation remain less clear. Previous studies identified social experience and pheromone signaling-dependent modulation of chromatin around behavioral switch gene fruitless, which encodes a transcription factor necessary and sufficient for male behaviors. To identify the molecular mechanisms driving social experience-dependent neuromodulation, we performed RNA-seq from antennal samples of mutant fruit flies in pheromone receptors and fruitless, as well as grouped or isolated wild-type males. We found that loss of pheromone detection differentially alters the levels of fruitless exons suggesting changes in splicing patterns. In addition, many Fruitless target neuromodulatory genes, such as neurotransmitter receptors, ion channels, and ion transporters, are differentially regulated by social context and pheromone signaling. Our results suggest that modulation of circuit activity and behaviors in response to social experience and pheromone signaling arise due to changes in transcriptional programs for neuromodulators downstream of behavioral switch gene function.

scholarly journals IDENTIFICATION OF BRAIN SITES CONTROLLING FEMALE RECEPTIVITY IN MOSAICS OF DROSOPHILA MELANOGASTER

Genetics ◽  
1983 ◽  
Vol 103 (2) ◽  
pp. 179-195
Author(s):  
Laurie Tompkins ◽  
Jeffrey C Hall
Keyword(s):  
Drosophila Melanogaster ◽  
Minimum Amount ◽  
Male Courtship ◽  
Experimental Conditions ◽  
Female Receptivity ◽  
Female Genotype ◽  
Courtship Behaviors ◽  
Necessary And Sufficient ◽  
The Brain ◽  
Male Genotype

ABSTRACT We have identified cells in the brain of Drosophila melanogaster that are required to be of female genotype for receptivity to copulation with males. To do this, we determined experimental conditions in which female flies virtually always copulate, then measured the minimum amount of male courtship that is required to stimulate females to indicate their receptivity to copulation. We then observed gynandromorphs with female genitalia to determine whether the sex mosaics elicited at least the minimum amount of courtship and, if so, whether they copulated. By analyzing these gynandromorphs, in which the genotype of external and internal tissues could be ascertained, we were able to identify a group of cells in the dorsal anterior brain that, when bilaterally female, is necessary and sufficient for receptivity to copulation. This group of cells is anatomically distinct from those that are required to be of male genotype for the performance of courtship behaviors.

Regulation of RUNX1 Transcriptional Function by GATA-1 Kinase Recruitment: A Novel Pathway for Megakaryocytic Gene Regulation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1183-1183
Author(s):  
Kamaleldin E. Elagib ◽  
Ivailo S. Mihaylov ◽  
Lorrie L. Delehanty ◽  
Sara L. Gonias ◽  
Jill F. Caronia ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Molecular Mechanisms ◽  
Wild Type ◽  
New Paradigm ◽  
Mobility Shift ◽  
Biochemical Basis ◽  
Cyclin Dependent Kinases ◽  
Functional Differences ◽  
Two Factors ◽  
Necessary And Sufficient

Abstract RUNX1 and GATA-1 both play essential roles in the transcriptional programming of normal mammalian megakaryocytic development, deficiencies of either factor having similar phenotypic consequences. We have previously characterized physical and functional interactions between these two factors, and others have confirmed analogous cooperations in Drosophila and Danio homologs. We now present data on molecular mechanisms for the cooperation of these two factors in the transcriptional activation of the megakaryocytic aIIb integrin promoter. In these studies, GATA-2 also physically interacted with RUNX1 but failed to cooperate in transcriptional activation. In fact, increasing amounts of GATA-2 repressed the functional interplay between GATA-1 and RUNX1. Through generation of GATA-2/GATA-1 chimeras, we identified a conserved subdomain within the GATA-1 amino terminus that was both necessary and sufficient for transcriptional cooperation with RUNX1. Coexpression of wild type GATA-1 or of cooperating GATA-2/GATA-1 chimeras, but not of GATA-2 or of non-cooperating chimeras, induced a mobility shift in wild type RUNX1. Using immunoprecipitation followed by immunoblot with a panel of phosphospecific antibodies, we found GATA-1 to induce RUNX1 phosphorylation at recognition sites for cyclin-dependent kinases (cdks). Treatment of cells with roscovitine, a specific cdk inhibitor, blocked the transcriptional cooperation of GATA-1 with RUNX1 and eliminated the RUNX1 mobility shift caused by GATA-1 coexpression. Mutagenesis of RUNX1 identified a cluster of serine/threonine-proline (S/TP) sites collectively required for the transcriptional augmentation and mobility shift induced by GATA-1. In addition, intact DNA binding by RUNX1 was required for cooperation with GATA-1. These results provide a new paradigm for cooperation of interacting transcription factors, in which one partner recruits a kinase leading to phosphorylation and activation of the other partner. Furthermore, these results provide a biochemical basis for the previously inexplicable functional differences between GATA-1, which promotes megakaryocytic maturation, and GATA-2 which promotes proliferation without maturation.

scholarly journals Chromatin-based reprogramming of a courtship regulator by concurrent pheromone perception and hormone signaling

2020 ◽  
Vol 6 (21) ◽  
pp. eaba6913 ◽  
Author(s):  
Songhui Zhao ◽  
Bryson Deanhardt ◽  
George Thomas Barlow ◽  
Paulina Guerra Schleske ◽  
Anthony M. Rossi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Behavioral Plasticity ◽  
Social Experience ◽  
Hormone Signaling ◽  
Active Chromatin ◽  
Simultaneous Exposure ◽  
Reproductive Behaviors ◽  
Courtship Behaviors ◽  
And Function ◽  
Pheromone Perception

To increase fitness, animals use both internal and external states to coordinate reproductive behaviors. The molecular mechanisms underlying this coordination remain unknown. Here, we focused on pheromone-sensing Drosophila Or47b neurons, which exhibit age- and social experience–dependent increase in pheromone responses and courtship advantage in males. FruitlessM (FruM), a master regulator of male courtship behaviors, drives the effects of social experience and age on Or47b neuron responses and function. We show that simultaneous exposure to social experience and age-specific juvenile hormone (JH) induces chromatin-based reprogramming of fruM expression in Or47b neurons. Group housing and JH signaling increase fruM expression in Or47b neurons and active chromatin marks at fruM promoter. Conversely, social isolation or loss of JH signaling decreases fruM expression and increases repressive marks around fruM promoter. Our results suggest that fruM promoter integrates coincident hormone and pheromone signals driving chromatin-based changes in expression and ultimately neuronal and behavioral plasticity.

scholarly journals Pheromones mediating copulation and attraction in Drosophila

2015 ◽  
Vol 112 (21) ◽  
pp. E2829-E2835 ◽  
Author(s):  
Hany K. M. Dweck ◽  
Shimaa A. M. Ebrahim ◽  
Michael Thoma ◽  
Ahmed A. M. Mohamed ◽  
Ian W. Keesey ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Methyl Palmitate ◽  
Mating Systems ◽  
Male Courtship ◽  
Level Information ◽  
Males And Females ◽  
Copulation Behavior ◽  
Attraction Behavior ◽  
Species Specific ◽  
Necessary And Sufficient

Intraspecific olfactory signals known as pheromones play important roles in insect mating systems. In the model Drosophila melanogaster, a key part of the pheromone-detecting system has remained enigmatic through many years of research in terms of both its behavioral significance and its activating ligands. Here we show that Or47b-and Or88a-expressing olfactory sensory neurons (OSNs) detect the fly-produced odorants methyl laurate (ML), methyl myristate, and methyl palmitate. Fruitless (fruM)-positive Or47b-expressing OSNs detect ML exclusively, and Or47b- and Or47b-expressing OSNs are required for optimal male copulation behavior. In addition, activation of Or47b-expressing OSNs in the male is sufficient to provide a competitive mating advantage. We further find that the vigorous male courtship displayed toward oenocyte-less flies is attributed to an oenocyte-independent sustained production of the Or47b ligand, ML. In addition, we reveal that Or88a-expressing OSNs respond to all three compounds, and that these neurons are necessary and sufficient for attraction behavior in both males and females. Beyond the OSN level, information regarding the three fly odorants is transferred from the antennal lobe to higher brain centers in two dedicated neural lines. Finally, we find that both Or47b- and Or88a-based systems and their ligands are remarkably conserved over a number of drosophilid species. Taken together, our results close a significant gap in the understanding of the olfactory background to Drosophila mating and attraction behavior; while reproductive isolation barriers between species are created mainly by species-specific signals, the mating enhancing signal in several Drosophila species is conserved.

scholarly journals Clostridium difficile exploits a host metabolite produced during toxin-mediated infection

2021 ◽  
Author(s):  
Kali M. Pruss ◽  
Justin L. Sonnenburg
Keyword(s):  
Clostridium Difficile ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Mouse Genetics ◽  
Enteric Pathogens ◽  
Rna Seq ◽  
Wild Type ◽  
Isogenic Mutant ◽  
Model Combining ◽  
The U.S

Several enteric pathogens can gain specific metabolic advantages over other members of the microbiota by inducing host pathology and inflammation. The pathogen Clostridium difficile (Cd) is responsible for a toxin-mediated colitis that causes 15,000 deaths in the U.S. yearly1, yet the molecular mechanisms by which Cd benefits from toxin-induced colitis remain understudied. Up to 21% of healthy adults are asymptomatic carriers of toxigenic Cd2, indicating that Cd can persist as part of a healthy microbiota; antibiotic-induced perturbation of the gut ecosystem is associated with transition to toxin-mediated disease. To understand how Cd metabolism adapts from a healthy gut to the inflamed conditions its toxins induce, we used RNA-seq to define the metabolic state of wild-type Cd versus an isogenic mutant lacking toxins in a mouse model. Combining bacterial and mouse genetics, we demonstrate that Cd utilizes sorbitol derived from both diet and host. Host-derived sorbitol is produced by the enzyme aldose reductase, which is expressed by diverse immune cells and is upregulated during inflammation, including during Cd toxin-mediated disease. This work highlights a mechanism by which Cd can utilize a host-derived nutrient generated during toxin-induced disease by an enzyme not previously associated with infection.

scholarly journals Insights into the roles of CMK-1 and OGT-1 in interstimulus interval-dependent habituation in Caenorhabditis elegans

2018 ◽  
Vol 285 (1891) ◽  
pp. 20182084 ◽  
Author(s):  
Evan L. Ardiel ◽  
Troy A. McDiarmid ◽  
Tiffany A. Timbers ◽  
Kirsten C. Y. Lee ◽  
Javad Safaei ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Sensory Neurons ◽  
Interstimulus Interval ◽  
Molecular Mechanisms ◽  
Dependent Manner ◽  
Short Isis ◽  
Wild Type ◽  
Conserved Genes ◽  
Rapid Stimulation ◽  
Glcnac Transferase

Habituation is a ubiquitous form of non-associative learning observed as a decrement in responding to repeated stimulation that cannot be explained by sensory adaptation or motor fatigue. One of the defining characteristics of habituation is its sensitivity to the rate at which training stimuli are presented—animals habituate faster in response to more rapid stimulation. The molecular mechanisms underlying this interstimulus interval (ISI)-dependent characteristic of habituation remain unknown. In this article, we use behavioural neurogenetic and bioinformatic analyses in the nematode Caenorhabiditis elegans to identify the first molecules that modulate habituation in an ISI-dependent manner. We show that the Caenorhabditis elegans orthologues of Ca 2+ /calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs. In addition, both cmk-1 and ogt-1 mutants display a rare mechanosensory hyper-responsive phenotype (i.e. larger mechanosensory responses than wild-type). Overall, our work identifies two conserved genes that function in sensory neurons to modulate habituation in an ISI-dependent manner, providing the first insights into the molecular mechanisms underlying the universally observed phenomenon that habituation has different properties when stimuli are delivered at different rates.

scholarly journals Transcriptome Dynamics of Double Recessive Mutant, o2o2o16o16, Reveals the Transcriptional Mechanisms in the Increase of Its Lysine and Tryptophan Content in Maize

Genes ◽  
2019 ◽  
Vol 10 (4) ◽  
pp. 316 ◽  
Author(s):  
Wei Wang ◽  
Yi Dai ◽  
Mingchun Wang ◽  
Wenpeng Yang ◽  
Degang Zhao
Keyword(s):  
Molecular Mechanisms ◽  
Degradation Pathway ◽  
Endosperm Development ◽  
Rna Seq ◽  
Wild Type ◽  
Genes Encoding ◽  
Recessive Mutant ◽  
Lysine Degradation ◽  
Tryptophan Content

In maize, pyramiding of o2 and o16 alleles can greatly improve the nutritional quality of grains. To dissect its molecular mechanism, we created a double recessive mutant line, o2o2o16o16, by introgression of the o2 and o16 alleles into the wild-type maize inbred line, by molecular marker-assisted backcross selection. The kernels (18 day after pollination (DAP), 28 DAP, and 38 DAP) of the o2o2o16o16 mutant and its parent lines were subject to RNA sequencing (RNA-Seq). The RNA-Seq analysis revealed that 59 differentially expressed genes (DEGs) were involved in lysine metabolism and 43 DEGs were involved in tryptophan metabolism. Among them, the genes encoding AK, ASADH, and Dap-F in the lysine synthesis pathway were upregulated at different stages of endosperm development, promoting the synthesis of lysine. Meanwhile, the genes encoding LKR/SDH and L-PO in the lysine degradation pathway were downregulated, inhibiting the degradation of lysine. Moreover, the genes encoding TAA and YUC in the tryptophan metabolic pathway were downregulated, restraining the degradation of tryptophan. Thus, pyramiding o2 and o16 alleles could increase the lysine and tryptophan content in maize. These above results would help to uncover the molecular mechanisms involved in the increase in lysine and the tryptophan content, through the introgression of o2 and o16 alleles into the wild-type maize.

scholarly journals Molecular Basis of p53 Functional Inactivation by the Leukemic Protein MLL-ELL

2003 ◽  
Vol 23 (12) ◽  
pp. 4230-4246 ◽  
Author(s):  
Dmitri Wiederschain ◽  
Hidehiko Kawai ◽  
JiJie Gu ◽  
Ali Shilatifard ◽  
Zhi-Min Yuan
Keyword(s):  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Cellular Transformation ◽  
Wild Type ◽  
Efficient Inhibitor ◽  
C Terminus ◽  
Functional Inactivation ◽  
Necessary And Sufficient ◽  
First Time

ABSTRACT The Eleven Lysine-rich Leukemia (ELL) gene undergoes translocation and fuses in frame to the Multiple Lineage Leukemia (MLL) gene in a substantial proportion of patients suffering from acute forms of leukemia. Molecular mechanisms of cellular transformation by the MLL-ELL fusion are not well understood. Although both MLL-ELL and wild-type ELL can reduce functional activity of p53 tumor suppressor, our data reveal that MLL-ELL is a much more efficient inhibitor of p53 than is wild-type ELL. We also demonstrate for the first time that ELL extreme C terminus [ELL(eCT)] is required for the recruitment of p53 into MLL-ELL nuclear foci and is both necessary and sufficient for the MLL-ELL inhibition of p53-mediated induction of p21 and apoptosis. Finally, our results demonstrate that MLL-ELL requires the presence of intact ELL(eCT) in order to disrupt p53 interactions with p300/CBP coactivator and thus significantly reduce p53 acetylation in vivo. Since ELL(eCT) has recently been shown to be both necessary and sufficient for MLL-ELL-mediated transformation of normal blood progenitors, our data correlate ELL(eCT) contribution to MLL-ELL transformative effects with its ability to functionally inhibit p53.

scholarly journals Transcriptional Regulation of the pdt Gene Cluster of Pseudomonas stutzeri KC Involves an AraC/XylS Family Transcriptional Activator (PdtC) and the Cognate Siderophore Pyridine-2,6-Bis(Thiocarboxylic Acid)

2006 ◽  
Vol 72 (11) ◽  
pp. 6994-7002 ◽  
Author(s):  
Sergio E. Morales ◽  
Thomas A. Lewis
Keyword(s):  
Gene Cluster ◽  
Molecular Mechanisms ◽  
Pseudomonas Stutzeri ◽  
Transcriptional Activator ◽  
Wild Type ◽  
Transcriptional Reporter ◽  
Reverse Transcription Pcr ◽  
Thiocarboxylic Acid ◽  
Transcriptional Units ◽  
Necessary And Sufficient

ABSTRACT In order to gain an understanding of the molecular mechanisms dictating production of the siderophore and dechlorination agent pyridine-2,6-bis(thiocarboxylic acid) (PDTC), we have begun characterization of a gene found in the pdt gene cluster of Pseudomonas stutzeri KC predicted to have a regulatory role. That gene product is an AraC family transcriptional activator, PdtC. Quantitative reverse transcription-PCR and expression of transcriptional reporter fusions were used to assess a role for pdtC in the transcription of pdt genes. PdtC and an upstream, promoter-proximal DNA segment were required for wild-type levels of expression from the promoter of a predicted biosynthesis operon (P pdt F ). At least two other transcriptional units within the pdt cluster were also dependent upon pdtC for expression at wild-type levels. The use of a heterologous, Pseudomonas putida host demonstrated that pdtC and an exogenously added siderophore were necessary and sufficient for expression from the pdtF promoter, i.e., none of the PDTC utilization genes within the pdt cluster were required for transcriptional signaling. Tests using the promoter of the pdtC gene in transcriptional reporter fusions indicated siderophore-dependent negative autoregulation similar to that seen with other AraC-type regulators of siderophore biosynthesis and utilization genes. The data increase the repertoire of siderophore systems known to be regulated by this type of transcriptional activator and have implications for PDTC signaling.

scholarly journals Cytological and transcriptome analyses reveal OsPUB73 defect affects the gene expression associated with tapetum or pollen exine abnormality in rice

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Lin Chen ◽  
Ruilian Deng ◽  
Guoqiang Liu ◽  
Jing Jin ◽  
Jinwen Wu ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Molecular Mechanisms ◽  
Rice Variety ◽  
Reproductive Development ◽  
Rna Seq ◽  
Wild Type ◽  
Pollen Exine ◽  
Polymerase Chain ◽  
Pollen Stage ◽  
Yield Decrease

Abstract Background As one of the main crops in the world, sterility of rice (Oryza sativa L.) significantly affects the production and leads to yield decrease. Our previous research showed that OsPUB73, which encodes U-box domain-containing protein 73, may be associated with male sterility. However, little information is available on this gene that is required for anther development. In the present study, we knocked out OsPUB73 by using the CRISPR/Cas9 system and studied the cytological and transcriptome of the gene-defect associated with pollen development and sterility in the rice variety (Taichung 65). Results The sequence analysis indicated that OsPUB73 was comprised of 3 exons and 2 introns, of which CDS encoded 586 amino acids including a U-box domain. The expression pattern of OsPUB73 showed that it was highly expressed in the anther during meiosis stage. The ospub73 displayed low pollen fertility (19.45%), which was significantly lower than wild type (WT) (85.37%). Cytological observation showed tapetum vacuolated at the meiosis stage and pollen exine was abnormal at the bi-cellular pollen stage of ospub73. RNA-seq analysis detected 2240 down and 571 up-regulated genes in anther of ospub73 compared with WT during meiosis stage. Among of 2240 down-regulated genes, seven known genes were associated with tapetal cell death or pollen exine development, including CYP703A3 (Cytochrome P450 Hydroxylase703A3), CYP704B2 (Cytochrome P450 Hydroxylase704B2), DPW (Defective Pollen Wall), PTC1 (Persistant Tapetal Cell1), UDT1 (Undeveloped Tapetum1), OsAP37 (Aspartic protease37) and OsABCG15 (ATP binding cassette G15), which were validated by quantitative real-time polymerase chain reaction (qRT-PCR). These results suggested OsPUB73 may play an important role in tapetal or pollen exine development and resulted in pollen partial sterility. Conclusion Our results revealed that OsPUB73 plays an important role in rice male reproductive development, which provides valuable information about the molecular mechanisms of the U-box in rice male reproductive development.

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