-
Genes, Brain, and Behavior Nov 2021Male sexual behavior in Drosophila melanogaster, largely controlled by the fruitless (fru) gene encoding the male specific Fru protein, is among the best studied animal... (Review)
Review
Male sexual behavior in Drosophila melanogaster, largely controlled by the fruitless (fru) gene encoding the male specific Fru protein, is among the best studied animal behaviors. Although substantial studies suggest that Fru specifies a neuronal circuitry governing all aspects of male sexual behaviors, recent findings show that Fru is not absolutely necessary for such behaviors. We propose that another regulatory gene doublesex encoding the male-specific Dsx protein builds a core neuronal circuitry that possesses the potential for courtship, which could be either induced through adult social experience or innately manifested during development by Fru expression in a broader neuronal circuitry. Fru expression levels and patterns determine the modes of courtship behavior from innate heterosexual, homosexual, bisexual, to learned courtship. We discuss how Fru expression is regulated by hormones and social experiences and tunes functional flexibility of the sex circuitry. We propose that regulatory genes hierarchically build the potential for innate and learned aspects of courtship behaviors, and expression changes of these regulatory genes among different individuals and species with different social experiences ultimately lead to behavioral diversification.
Topics: Animals; DNA-Binding Proteins; Drosophila Proteins; Drosophila melanogaster; Female; Male; Mating Preference, Animal; Nerve Tissue Proteins; Neurons; Transcription Factors
PubMed: 34672079
DOI: 10.1111/gbb.12772 -
Cell Reports Nov 2023Tumor-suppressive cell competition (TSCC) is a conserved surveillance mechanism in which neighboring cells actively eliminate oncogenic cells. Despite overwhelming...
Tumor-suppressive cell competition (TSCC) is a conserved surveillance mechanism in which neighboring cells actively eliminate oncogenic cells. Despite overwhelming studies showing that the unfolded protein response (UPR) is dysregulated in various tumors, it remains debatable whether the UPR restrains or promotes tumorigenesis. Here, using Drosophila eye epithelium as a model, we uncover a surprising decisive role of the Ire1 branch of the UPR in regulating cell polarity gene scribble (scrib) loss-induced TSCC. Both mutation and hyperactivation of Ire1 accelerate elimination of scrib clones via inducing apoptosis and autophagy, respectively. Unexpectedly, relative Ire1 activity is also crucial for determining loser cell fate, as dysregulating Ire1 signaling in the surrounding healthy cells reversed the "loser" status of scrib clones by decreasing their apoptosis. Furthermore, we show that Ire1 is required for cell competition in mammalian cells. Together, these findings provide molecular insights into scrib-mediated TSCC and highlight Ire1 as a key determinant of loser cell fate.
Topics: Animals; Cell Competition; Drosophila; Drosophila Proteins; Mammals; Neoplasms; Signal Transduction; Unfolded Protein Response
PubMed: 37924514
DOI: 10.1016/j.celrep.2023.113303 -
Genes Feb 2020Behavior is a readout of neural function. Therefore, any difference in behavior among different species is, in theory, an outcome of interspecies diversification in the... (Review)
Review
Behavior is a readout of neural function. Therefore, any difference in behavior among different species is, in theory, an outcome of interspecies diversification in the structure and/or function of the nervous system. However, the neural diversity underlying the species-specificity in behavioral traits and its genetic basis have been poorly understood. In this article, we discuss potential neural substrates for species differences in the courtship pulse song frequency and mating partner choice in the subgroup. We also discuss possible neurogenetic mechanisms whereby a novel behavioral repertoire emerges based on the study of nuptial gift transfer, a trait unique to in the genus . We found that the conserved central circuit composed primarily of -expressing neurons (the -circuit) serves for the execution of courtship behavior, whereas the sensory pathways impinging onto the -circuit or the motor pathways downstream of the -circuit are susceptible to changes associated with behavioral species differences.
Topics: Animals; Drosophila Proteins; Drosophila melanogaster; Neural Pathways; Neurons; Sexual Behavior, Animal
PubMed: 32024133
DOI: 10.3390/genes11020157 -
Nature Communications Mar 2022Carbohydrates, proteins and lipids are essential nutrients to all animals; however, closely related species, populations, and individuals can display dramatic variation...
Carbohydrates, proteins and lipids are essential nutrients to all animals; however, closely related species, populations, and individuals can display dramatic variation in diet. Here we explore the variation in macronutrient tolerance in Drosophila melanogaster using the Drosophila genetic reference panel, a collection of ~200 strains derived from a single natural population. Our study demonstrates that D. melanogaster, often considered a "dietary generalist", displays marked genetic variation in survival on different diets, notably on high-sugar diet. Our genetic analysis and functional validation identify several regulators of macronutrient tolerance, including CG10960/GLUT8, Pkn and Eip75B. We also demonstrate a role for the JNK pathway in sugar tolerance and de novo lipogenesis. Finally, we report a role for tailless, a conserved orphan nuclear hormone receptor, in regulating sugar metabolism via insulin-like peptide secretion and sugar-responsive CCHamide-2 expression. Our study provides support for the use of nutrigenomics in the development of personalized nutrition.
Topics: Animals; DNA-Binding Proteins; Drosophila Proteins; Drosophila melanogaster; Genetic Variation; Nutrients; Sugars; Transcription Factors
PubMed: 35347148
DOI: 10.1038/s41467-022-29183-x -
Neuroscience Research May 2024DSCAM (Down syndrome cell adhesion molecule) is a unique neuronal adhesion protein with extensively documented multifaceted functionalities. DSCAM also has interesting... (Review)
Review
DSCAM (Down syndrome cell adhesion molecule) is a unique neuronal adhesion protein with extensively documented multifaceted functionalities. DSCAM also has interesting properties in vertebrates and invertebrates, respectively. In Drosophila species, particularly, Dscam exhibits remarkable genetic diversity, with tens of thousands of splicing isoforms that modulate the specificity of neuronal wiring. Interestingly, this splice variant diversity of Dscam is absent in vertebrates. DSCAM plays a pivotal role in mitigating excessive adhesion between identical cell types, thereby maintaining the structural and functional coherence of neural networks. DSCAM contributes to the oversight of selective intercellular interactions such as synaptogenesis; however, the precise regulatory mechanisms underlying the promotion and inhibition of cell adhesion involved remain unclear. In this review, we aim to delineate the distinct molecules that interact with DSCAM and their specific roles within the biological landscapes of Drosophila and vertebrates. By integrating these comparative insights, we aim to elucidate the multifunctional nature of DSCAM, particularly its capacity to facilitate or deter intercellular adhesion.
Topics: Animals; Cell Adhesion Molecules; Drosophila; Vertebrates; Drosophila Proteins; Humans; Cell Adhesion; Neurons
PubMed: 38141781
DOI: 10.1016/j.neures.2023.12.005 -
Development (Cambridge, England) Sep 2019Junctional complexes that mediate cell adhesion are key to epithelial integrity, cell division and permeability barrier formation. In , the scaffolding proteins Scribble...
Junctional complexes that mediate cell adhesion are key to epithelial integrity, cell division and permeability barrier formation. In , the scaffolding proteins Scribble (Scrib) and Discs Large (Dlg) are key regulators of epithelial polarity, proliferation, assembly of junctions and protein trafficking. We found that Scrib and Dlg are necessary for the formation of the tricellular junction (TCJ), a unique junction that forms in epithelia at the point of convergence of three neighboring cells. Scrib and Dlg are in close proximity with the TCJ proteins Gliotactin (Gli) and Bark Beetle (Bark), and both are required for TCJ protein recruitment. Loss of Bark or Gli led to basolateral spread of the TCJ complex at the cell corners. Loss of the septate junction proteins Nrx-IV and the Na/K ATPase also resulted in basolateral spread of the entire TCJ complex at the cell corners. The Scrib PDZ1-2 domains and the Dlg GUK domain are necessary for Bark and Gli localization to the TCJ. Overall, we propose a model in which Scrib and Dlg are key components of the TCJ, and form a complex with Bark and Gli.
Topics: Animals; Drosophila Proteins; Drosophila melanogaster; Gene Knockdown Techniques; Intercellular Junctions; Membrane Proteins; Protein Domains; Tumor Suppressor Proteins
PubMed: 31444218
DOI: 10.1242/dev.174763 -
Life Science Alliance May 2024Ciliary defects cause several ciliopathies, some of which have late onset, suggesting cilia are actively maintained. Still, we have a poor understanding of the...
Ciliary defects cause several ciliopathies, some of which have late onset, suggesting cilia are actively maintained. Still, we have a poor understanding of the mechanisms underlying their maintenance. Here, we show r IFT88 (IFT88/nompB) continues to move along fully formed sensory cilia. We further identify Inactive, a TRPV channel subunit involved in hearing and negative-gravitaxis behaviour, and a yet uncharacterised Guanylyl Cyclase 2d (Gucy2d/CG34357) as IFT88 cargoes. We also show IFT88 binding to the cyclase´s intracellular part, which is evolutionarily conserved and mutated in several degenerative retinal diseases, is important for the ciliary localisation of Gucy2d. Finally, acute knockdown of both IFT88 and Gucy2d in ciliated neurons of adult flies caused defects in the maintenance of cilium function, impairing hearing and negative-gravitaxis behaviour, but did not significantly affect ciliary ultrastructure. We conclude that the sensory ciliary function underlying hearing in the adult fly requires an active maintenance program which involves IFT88 and at least two of its signalling transmembrane cargoes, Gucy2d and Inactive.
Topics: Animals; Drosophila; Cilia; Drosophila melanogaster; Drosophila Proteins; Hearing
PubMed: 38373798
DOI: 10.26508/lsa.202302289 -
The EMBO Journal Jun 2020Immune cells provide defense against non-self and have recently been shown to also play key roles in diverse processes such as development, metabolism, and tumor...
Immune cells provide defense against non-self and have recently been shown to also play key roles in diverse processes such as development, metabolism, and tumor progression. The heterogeneity of Drosophila immune cells (hemocytes) remains an open question. Using bulk RNA sequencing, we find that the hemocytes display distinct features in the embryo, a closed and rapidly developing system, compared to the larva, which is exposed to environmental and metabolic challenges. Through single-cell RNA sequencing, we identify fourteen hemocyte clusters present in unchallenged larvae and associated with distinct processes, e.g., proliferation, phagocytosis, metabolic homeostasis, and humoral response. Finally, we characterize the changes occurring in the hemocyte clusters upon wasp infestation, which triggers the differentiation of a novel hemocyte type, the lamellocyte. This first molecular atlas of hemocytes provides insights and paves the way to study the biology of the Drosophila immune cells in physiological and pathological conditions.
Topics: Animals; Drosophila Proteins; Drosophila melanogaster; Hemocytes; Larva
PubMed: 32162708
DOI: 10.15252/embj.2020104486 -
Developmental Cell Jun 2021Toll receptors are key determinants of planar polarity during Drosophila gastrulation. Two papers in the current issue of Developmental Cell now identify key features of...
Toll receptors are key determinants of planar polarity during Drosophila gastrulation. Two papers in the current issue of Developmental Cell now identify key features of their downstream signaling that allow cell symmetry to be broken by apparently non-polarized Toll receptors.
Topics: Animals; Drosophila; Drosophila Proteins; Gastrulation; Signal Transduction
PubMed: 34102101
DOI: 10.1016/j.devcel.2021.05.013 -
Genetics Mar 2021The evolutionarily conserved Roundabout (Robo) family of axon guidance receptors control midline crossing of axons in response to the midline repellant ligand Slit in...
The evolutionarily conserved Roundabout (Robo) family of axon guidance receptors control midline crossing of axons in response to the midline repellant ligand Slit in bilaterian animals including insects, nematodes, and vertebrates. Despite this strong evolutionary conservation, it is unclear whether the signaling mechanism(s) downstream of Robo receptors are similarly conserved. To directly compare midline repulsive signaling in Robo family members from different species, here we use a transgenic approach to express the Robo family receptor SAX-3 from the nematode Caenorhabditis elegans in neurons of the fruit fly, Drosophila melanogaster. We examine SAX-3's ability to repel Drosophila axons from the Slit-expressing midline in gain of function assays, and test SAX-3's ability to substitute for Drosophila Robo1 during fly embryonic development in genetic rescue experiments. We show that C. elegans SAX-3 is properly translated and localized to neuronal axons when expressed in the Drosophila embryonic CNS, and that SAX-3 can signal midline repulsion in Drosophila embryonic neurons, although not as efficiently as Drosophila Robo1. Using a series of Robo1/SAX-3 chimeras, we show that the SAX-3 cytoplasmic domain can signal midline repulsion to the same extent as Robo1 when combined with the Robo1 ectodomain. We show that SAX-3 is not subject to endosomal sorting by the negative regulator Commissureless (Comm) in Drosophila neurons in vivo, and that peri-membrane and ectodomain sequences are both required for Comm sorting of Drosophila Robo1.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Conserved Sequence; Drosophila Proteins; Drosophila melanogaster; Endosomes; Evolution, Molecular; Genetic Complementation Test; Membrane Proteins; Nerve Tissue Proteins; Neurons; Protein Transport; Receptors, Immunologic; Signal Transduction; Roundabout Proteins
PubMed: 33789352
DOI: 10.1093/genetics/iyab018