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Biochemical Society Transactions Aug 2020Pygo is a nuclear protein containing two conserved domains, NHD and PHD, which play important roles in embryonic development and carcinogenesis. Pygo was first... (Review)
Review
Pygo is a nuclear protein containing two conserved domains, NHD and PHD, which play important roles in embryonic development and carcinogenesis. Pygo was first identified as a core component of the Wnt/β-catenin signalling pathway. However, it has also been reported that the function of Pygo is not always Wnt/β-catenin signalling dependent. In this review, we summarise the functions of both domains of Pygo and show that their functions are synergetic. The PHD domain mainly combines with transcription co-factors, including histone 3 and Bcl9/9l. The NHD domain mainly recruits histone methyltransferase/acetyltransferase (HMT/HAT) to modify lysine 4 of the histone 3 tail (H3K4) and interacts with Chip/LIM-domain DNA-binding proteins (ChiLS) to form enhanceosomes to regulate transcriptional activity. Furthermore, we summarised chromatin modification differences of Pygo in Drosophila (dPygo) and vertebrates, and found that Pygo displayes a chromatin silencing function in Drosophila, while in vertebates, Pygo has a chromatin-activating function due to the two substitution of two amino acid residues. Next, we confirmed the relationship between Pygo and Bcl9/9l and found that Pygo-Bcl/9l are specifically partnered both in the nucleus and in the cytoplasm. Finally, we discuss whether transcriptional activity of Pygo is Wnt/β-catenin dependent during embryonic development. Available information indications that the transcriptional activity of Pygo in embryonic development is either Wnt/β-catenin dependent or independent in both tissue-specific and cell-specific-modes.
Topics: Animals; Drosophila Proteins; Drosophila melanogaster; Gene Silencing; Histone Acetyltransferases; Histone Methyltransferases; Intracellular Signaling Peptides and Proteins; Protein Conformation; Protein Domains; Wnt Proteins; Wnt Signaling Pathway; beta Catenin
PubMed: 32677664
DOI: 10.1042/BST20200393 -
Current Biology : CB Aug 2023Bilateral symmetry defines much of the animal kingdom and is crucial for numerous functions of bilaterian organisms. Genetic approaches have discovered highly conserved...
Bilateral symmetry defines much of the animal kingdom and is crucial for numerous functions of bilaterian organisms. Genetic approaches have discovered highly conserved patterning networks that establish bilateral symmetry in early embryos, but how this symmetry is maintained throughout subsequent morphogenetic events remains largely unknown. Here we show that the terminal patterning system-which relies on Ras/ERK signaling through activation of the Torso receptor by its ligand Trunk-is critical for preserving bilateral symmetry during Drosophila body axis elongation, a process driven by cell rearrangements in the two identical lateral regions of the embryo and specified by the dorsal-ventral and anterior-posterior patterning systems. We demonstrate that fluctuating asymmetries in this rapid convergent-extension process are attenuated in normal embryos over time, possibly through noise-dissipating forces from the posterior midgut invagination and movement. However, when Torso signaling is attenuated via mutation of Trunk or RNAi directed against downstream Ras/ERK pathway components, body axis elongation results in a characteristic corkscrew phenotype, which reflects dramatic reorganization of global tissue flow and is incompatible with viability. Our results reveal a new function downstream of the Drosophila terminal patterning system in potentially active control of bilateral symmetry and should motivate systematic search for similar symmetry-preserving regulatory mechanisms in other bilaterians.
Topics: Animals; Body Patterning; Morphogenesis; Drosophila; Drosophila Proteins; Gastrulation; Gene Expression Regulation, Developmental; Embryo, Nonmammalian
PubMed: 37562404
DOI: 10.1016/j.cub.2023.07.050 -
Current Opinion in Insect Science Oct 2021During development, the insect Malpighian tubule undergoes several programmed morphogenetic events that give rise to the tubule's ability to transport ions and water at... (Review)
Review
During development, the insect Malpighian tubule undergoes several programmed morphogenetic events that give rise to the tubule's ability to transport ions and water at unparalleled speed. Studies in Diptera, in particular, have greatly increased our understanding of the molecular pathways underlying embryonic tubule development. In this review, we discuss recent work that has revealed new insights into the molecular players required for the development and maintenance of structurally and functionally intact adult Malpighian tubules. We highlight the contribution of the smooth septate junction (sSJ) proteins to the morphogenesis and transport function of the epithelial cells of the Drosophila melanogaster Malpighian tubule and also discuss new findings on the role of the GATAe transcription factor. We also consider the roles of sSJ proteins in the fly midgut, as compared to the Malpighian tubule, and the importance of cellular context for the functions of these proteins.
Topics: Animals; Drosophila Proteins; Drosophila melanogaster; Embryonic Development; GATA Transcription Factors; Ion Transport; Malpighian Tubules; Morphogenesis
PubMed: 33581351
DOI: 10.1016/j.cois.2021.02.001 -
Fly Dec 2022Notch signalling is a well-conserved signalling pathway that regulates cell fate through cell-cell communication. A typical feature of Notch signalling is 'lateral... (Review)
Review
Notch signalling is a well-conserved signalling pathway that regulates cell fate through cell-cell communication. A typical feature of Notch signalling is 'lateral inhibition', whereby two neighbouring cells of equivalent state of differentiation acquire different cell fates. Recently, mathematical and computational approaches have addressed the Notch dynamics in neural development. Typical examples of lateral inhibition are observed in the specification of neural stem cells in the embryo and sensory organ precursors in the thorax. In eye disc development, Notch signalling cooperates with other signalling pathways to define the evenly spaced positioning of the photoreceptor cells. The interplay between Notch and epidermal growth factor receptor signalling regulates the timing of neural stem cell differentiation in the optic lobe. In this review, we summarize the theoretical studies that have been conducted to elucidate the Notch dynamics in these systems and discuss the advantages of combining mathematical models with biological experiments.
Topics: Animals; Cell Differentiation; Drosophila; Drosophila Proteins; Membrane Proteins; Models, Theoretical; Receptors, Notch
PubMed: 34609265
DOI: 10.1080/19336934.2021.1953363 -
The European Journal of Neuroscience Jan 2020A central question in the circadian biology field concerns the mechanisms that translate ~24-hr oscillations of the molecular clock into overt rhythms. Drosophila... (Review)
Review
A central question in the circadian biology field concerns the mechanisms that translate ~24-hr oscillations of the molecular clock into overt rhythms. Drosophila melanogaster is a powerful system that provided the first understanding of how molecular clocks are generated and is now illuminating the neural basis of circadian behavior. The identity of ~150 clock neurons in the Drosophila brain and their roles in shaping circadian rhythms of locomotor activity have been described before. This review summarizes mechanisms that transmit time-of-day signals from the clock, within the clock network as well as downstream of it. We also discuss the identification of functional multisynaptic circuits between clock neurons and output neurons that regulate locomotor activity.
Topics: Animals; Brain; Circadian Clocks; Circadian Rhythm; Drosophila; Drosophila Proteins; Drosophila melanogaster
PubMed: 30059181
DOI: 10.1111/ejn.14092 -
Fly Dec 2022Receptor proteins of the Roundabout (Robo) family regulate axon guidance decisions during nervous system development. Among the three family genes ( and displays a...
Receptor proteins of the Roundabout (Robo) family regulate axon guidance decisions during nervous system development. Among the three family genes ( and displays a dynamic expression pattern and regulates multiple axon guidance outcomes, including preventing midline crossing in some axons, promoting midline crossing in others, forming lateral longitudinal axon pathways, and regulating motor axon guidance. The identity and location of enhancer elements regulating complex and dynamic expression pattern in different neural cell types are unknown. Here, we characterize a set of 17 transgenic lines expressing GAL4 under the control of DNA sequences derived from noncoding regions in and around , to identify enhancers controlling specific aspects of expression in the embryonic ventral nerve cord. We identify individual fragments that confer expression in specific cell types where is known to function, including early pioneer neurons, midline glia and lateral longitudinal neurons. Our results indicate that s dynamic expression pattern is specified by a combination of enhancer elements that are active in different subsets of cells. We show that expression in lateral longitudinal axons represents two genetically separable subsets of neurons, and compare their axon projections with each other and with Fasciclin II (FasII), a commonly used marker of longitudinal axon pathways. In addition, we provide a general description of each fragment's expression in embryonic tissues outside of the nervous system, to serve as a resource for other researchers interested in expression and its functional roles outside the central nervous system.
Topics: Animals; Axons; Drosophila; Drosophila Proteins; Gene Expression Regulation, Developmental; Nerve Tissue Proteins; Receptors, Immunologic
PubMed: 36217698
DOI: 10.1080/19336934.2022.2126259 -
Genome Dec 2022Autophagy is an important process that maintains adult tissue homeostasis and functions by protecting cells in autonomous and non-cell-autonomous ways. By degrading... (Review)
Review
Autophagy is an important process that maintains adult tissue homeostasis and functions by protecting cells in autonomous and non-cell-autonomous ways. By degrading toxic components or proteins involved in cell signaling pathways, autophagy preserves the balance among stem cells, progenitors, and differentiated cells in various tissues. In this minireview, we discuss recent studies performed in that highlight new roles of autophagy in adult cell fate decisions, including quiescence, proliferation, differentiation, and death.
Topics: Animals; Drosophila; Cell Differentiation; Autophagy; Stem Cells; Drosophila Proteins
PubMed: 36240515
DOI: 10.1139/gen-2022-0069 -
Current Topics in Developmental Biology 2020The notion that graded distributions of signals underlie the spatial organization of biological systems has long been a central pillar in the fields of cell and... (Review)
Review
The notion that graded distributions of signals underlie the spatial organization of biological systems has long been a central pillar in the fields of cell and developmental biology. During morphogenesis, morphogens spread across tissues to guide development of the embryo. Similarly, a variety of dynamic gradients and pattern-forming networks have been discovered that shape subcellular organization. Here we discuss the principles of intracellular pattern formation by these intracellular morphogens and relate them to conceptually similar processes operating at the tissue scale. We will specifically review mechanisms for generating cellular asymmetry and consider how intracellular patterning networks are controlled and adapt to cellular geometry. Finally, we assess the general concept of intracellular gradients as a mechanism for positional control in light of current data, highlighting how the simple readout of fixed concentration thresholds fails to fully capture the complexity of spatial patterning processes occurring inside cells.
Topics: Animals; Body Patterning; Drosophila Proteins; Drosophila melanogaster; Embryo, Nonmammalian; Gene Expression Regulation, Developmental; Models, Biological; Subcellular Fractions
PubMed: 32143745
DOI: 10.1016/bs.ctdb.2019.11.006 -
ELife Jun 2023Communication between distant cells can be mediated by extracellular vesicles (EVs) that deliver proteins and RNAs to recipient cells. Little is known about how EVs are...
Communication between distant cells can be mediated by extracellular vesicles (EVs) that deliver proteins and RNAs to recipient cells. Little is known about how EVs are targeted to specific cell types. Here, we identify the cell-surface protein Stranded at second (Sas) as a targeting ligand for EVs. Full-length Sas is present in EV preparations from transfected Schneider 2 (S2) cells. Sas is a binding partner for the Ptp10D receptor tyrosine phosphatase, and Sas-bearing EVs preferentially target to cells expressing Ptp10D. We used co-immunoprecipitation and peptide binding to show that the cytoplasmic domain (ICD) of Sas binds to dArc1 and mammalian Arc. dArc1 and Arc are related to retrotransposon Gag proteins. They form virus-like capsids which encapsulate and other mRNAs and are transported between cells via EVs. The Sas ICD contains a motif required for dArc1 binding that is shared by the mammalian and amyloid precursor protein (APP) orthologs, and the APP ICD also binds to mammalian Arc. Sas facilitates delivery of dArc1 capsids bearing mRNA into distant Ptp10D-expressing recipient cells in vivo.
Topics: Animals; Ligands; Extracellular Vesicles; Drosophila; Membrane Proteins; Drosophila Proteins; RNA, Messenger; Mammals
PubMed: 37326306
DOI: 10.7554/eLife.82874 -
Cell Reports Nov 2023Most epithelial tissues are maintained by stem cells that produce the different cell lineages required for proper tissue function. Constant communication between...
Most epithelial tissues are maintained by stem cells that produce the different cell lineages required for proper tissue function. Constant communication between different cell types ensures precise regulation of stem cell behavior and cell fate decisions. These cell-cell interactions are often disrupted during tumorigenesis, but mechanisms by which they are co-opted to support tumor growth in different genetic contexts are poorly understood. Here, we introduce PromoterSwitch, a genetic platform we established to generate large, transformed clones derived from individual adult Drosophila intestinal stem/progenitor cells. We show that cancer-driving genetic alterations representing common colon tumor genome landscapes disrupt cell fate decisions within transformed tissue and result in the emergence of abnormal cell fates. We also show that transformed enteroendocrine cells, a differentiated, hormone-secreting cell lineage, support tumor growth by regulating intestinal stem cell proliferation through multiple genotype-dependent mechanisms, which represent potential vulnerabilities that could be exploited for therapy.
Topics: Animals; Drosophila; Signal Transduction; Intestines; Cell Differentiation; Enteroendocrine Cells; Cell Lineage; Drosophila Proteins; Carcinogenesis; Neoplasms
PubMed: 37924517
DOI: 10.1016/j.celrep.2023.113370