Expression of Transposable Elements in the Brain of the Drosophila melanogaster Model for Fragile X Syndrome DOI Open Access

Maria Dolores De Donno,

Antonietta Puricella,

Simona D’Attis

et al.

Genes, Journal Year: 2023, Volume and Issue: 14(5), P. 1060 - 1060

Published: May 9, 2023

Fragile X syndrome is a neuro-developmental disease affecting intellectual abilities and social interactions. Drosophila melanogaster represents consolidated model to study neuronal pathways underlying this syndrome, especially because the recapitulates complex behavioural phenotypes. protein, or FMRP, required for normal structure correct synaptic differentiation in both peripheral central nervous systems, as well connectivity during development of circuits. At molecular level, FMRP has crucial role RNA homeostasis, including transposon regulation gonads D. m. Transposons are repetitive sequences regulated at transcriptional post-transcriptional levels avoid genomic instability. De-regulation transposons brain response chromatin relaxation previously been related neurodegenerative events models. Here, we demonstrate first time that silencing larval adult brains “loss function” dFmr1 mutants. This highlights flies kept isolation, defined asocial conditions, experience activation transposable elements. In all, these results suggest pathogenesis certain neurological alterations abnormal behaviors.

Language: Английский

Experience-dependent glial pruning of synaptic glomeruli during the critical period DOI Creative Commons

Nichalas Nelson,

Dominic J. Vita, Kendal Broadie

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: April 20, 2024

Abstract Critical periods are temporally-restricted, early-life windows when sensory experience remodels synaptic connectivity to optimize environmental input. In the Drosophila juvenile brain, critical period drives synapse elimination, which is transiently reversible. Within olfactory neuron (OSN) classes synapsing onto single projection neurons extending brain learning/memory centers, we find glia mediate experience-dependent pruning of OSN glomeruli downstream odorant exposure. We glial projections infiltrate neuropil in response experience, and use Draper (MEGF10) engulfment receptors prune glomeruli. Downstream, antagonistic Basket (JNK) Puckered (DUSP) signaling required for translocation activated into nuclei. Dependent on this signaling, expression F-actin linking scaffold Cheerio (FLNA), absolutely essential pruning. mediates regulation cytoskeleton remodeling. These results define a sequential pathway strictly-defined period; input infiltration projections, Draper/MEGF10 activate Basket/JNK cascade transcriptional activation, Cheerio/FLNA induction regulates actin targeted phagocytosis.

Language: Английский

Citations

11
Experience-dependent MAPK/ERK signaling in glia regulates critical period remodeling of synaptic glomeruli DOI Creative Commons

Nicholas Baumann,

James C. Sears, Kendal Broadie

et al.

Cellular Signalling, Journal Year: 2024, Volume and Issue: 120, P. 111224 - 111224

Published: May 12, 2024

Early-life critical periods allow initial sensory experience to remodel brain circuitry so that synaptic connectivity can be optimized environmental input. In the Drosophila juvenile brain, olfactory neuron (OSN) glomeruli are pruned by glial phagocytosis in dose-dependent response early odor during a well-defined period. Extracellular signal-regulated kinase (ERK) separation of phases-based activity reporter (SPARK) biosensors reveal experience-dependent signaling glia this Glial ERK-SPARK is depressed removal Draper receptors orchestrating phagocytosis. Cell-targeted genetic knockdown ERK reduces pruning OSN mechanism. Noonan Syndrome caused gain-of-function mutations protein tyrosine phosphatase non-receptor type 11 (PTPN11) inhibiting signaling, and glial-targeted patient-derived mutation increases impairs glomeruli. We conclude period drives required for glomeruli, altered mechanism disease model.

Language: Английский

Citations

7
Neuron-to-glia and glia-to-glia signaling directs critical period experience-dependent synapse pruning DOI Creative Commons

Nichalas Nelson,

Vanessa Miller, Kendal Broadie

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 18, 2025

Experience-dependent glial synapse pruning plays a pivotal role in sculpting brain circuit connectivity during early-life critical periods of development. Recent advances suggest layered cascade intercellular communication between neurons and phagocytes orchestrates this precise, targeted elimination. We focus here on studies from the powerful Drosophila forward genetic model, with reference to complementary findings mouse work. present both neuron-to-glia glia-to-glia signaling pathways directing experience-dependent pruning. discuss putative hierarchy secreted long-distance cues cell surface short-distance that act sequentially orchestrate glia activation, infiltration, target recognition, engulfment, then phagocytosis for Ligand-receptor partners mediating these stages different contexts are discussed recent studies. Signaling include phospholipids, small neurotransmitters, insulin-like peptides, proteins. Conserved receptors ligands discussed, together mechanisms where receptor identity remains unknown. Potential proposed tight temporal-restriction heightened elimination periods, as well potential means re-open such plasticity at maturity.

Language: Английский

Citations

0
Developmental deletion of amyloid precursor protein precludes transcriptional and proteomic responses to brain injury DOI Creative Commons
Valentina Lacovich, Mária Čarná,

Sebastian J. Novotný

et al.

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(4)

Published: April 1, 2025

Abstract INTRODUCTION Amyloid precursor protein (APP) undergoes striking changes following traumatic brain injury (TBI). Considering its role in the control of gene expression, we investigated whether APP regulates transcription and translation TBI. METHODS We assessed morphology ( n = 4–9 mice/group), transcriptome 3 proteome behavior 17–27 mice/group) wild‐type (WT) knock‐out (KO) mice either untreated or 10‐weeks RESULTS After TBI, WT displayed transcriptional programs consistent with late stages repair, hub genes were predicted to impact showed subtle changes. KO largely replicated this repertoire, but no nor translational response DISCUSSION The similarities between TBI suggest that developmental deficiency induces a condition reminiscent hampering expression injury. Highlights after brains exhibit profiles stage repair. Developmental maintains perpetually an immature state akin responds by at level. precludes molecular

Language: Английский

Citations

0
Role of fragile X messenger ribonucleoprotein 1 in the pathophysiology of brain disorders: a glia perspective DOI Creative Commons
Simona D’Antoni, Michela Spatuzza, C. Bonaccorso

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 162, P. 105731 - 105731

Published: May 18, 2024

Fragile X messenger ribonucleoprotein 1 (FMRP) is a widely expressed RNA binding protein involved in several steps of mRNA metabolism. Mutations the FMR1 gene encoding FMRP are responsible for fragile syndrome (FXS), leading genetic cause intellectual disability and autism spectrum disorder, X-associated tremor-ataxia (FXTAS), neurodegenerative disorder aging men. Although mainly neurons, it also present glial cells its deficiency or altered expression can affect functions with implications pathophysiology brain disorders. The review focuses on recent advances role subtypes, astrocytes, oligodendrocytes microglia, FXS FXTAS, describes how absence reduced these impact neuronal functions. We will briefly address radial effects neural development gliomas speculate other

Language: Английский

Citations

2
Experience-dependent serotonergic signaling in glia regulates targeted synapse elimination DOI Creative Commons
Vanessa Miller, Kendal Broadie

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(10), P. e3002822 - e3002822

Published: Oct. 1, 2024

The optimization of brain circuit connectivity based on initial environmental input occurs during critical periods characterized by sensory experience-dependent, temporally restricted, and transiently reversible synapse elimination. This precise, targeted synaptic pruning mechanism is mediated glial phagocytosis. Serotonin signaling has prominent, foundational roles in the brain, but functions glia, or experience-dependent remodeling, have been relatively unknown. Here, we discover that serotonergic between glia essential for olfactory glomerulus restricted to a well-defined Drosophila period. We find serotonin period, with both (1) production (2) 5-HT 2A receptors specifically not neurons, absolutely required pruning. receptor limits period conditional reexpression within adult reestablishes “critical period-like” at maturity. These results reveal an requirement

Language: Английский

Citations

1
Absence of pretaporter restrains features of the parkin phenotype in Drosophila DOI

María Constanza Silvera,

Rafael Cantera,

M.J. Ferreiro

et al.

Experimental Neurology, Journal Year: 2024, Volume and Issue: 383, P. 114997 - 114997

Published: Oct. 10, 2024

Language: Английский

Citations

1
Decoding Nucleotide Repeat Expansion Diseases: Novel Insights from Drosophila melanogaster Studies DOI Open Access
Sandra Atienzar‐Aroca,

Marleen Kat,

Arturo López Castel

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11794 - 11794

Published: Nov. 2, 2024

Drosophila melanogaster usage has provided substantial insights into the pathogenesis of several nucleotide repeat expansion diseases (NREDs), a group genetic characterized by abnormal DNA repeats. Leveraging simplicity and manipulability Drosophila, researchers have successfully modeled close to 15 NREDs such as Huntington’s disease (HD), spinocerebellar ataxias (SCA), myotonic dystrophies type 1 2 (DM1/DM2). These models been instrumental in characterizing principal associated molecular mechanisms: protein aggregation, RNA toxicity, function loss, thus recapitulating key features human disease. Used chemical screenings, they also enable us identify promising small molecules modifiers that mitigate toxic effects expanded This review summarizes 150 studies performed this area during last seven years. The relevant highlights are achievement first fly-based for some NREDs, incorporation new technologies CRISPR developing or evaluating transgenic flies containing motifs, evaluation less understood mechanisms RAN translation. Overall, remains powerful platform research NREDs.

Language: Английский

Citations

0
Expression of Transposable Elements in the Brain of the Drosophila melanogaster Model for Fragile X Syndrome DOI Open Access

Maria Dolores De Donno,

Antonietta Puricella,

Simona D’Attis

et al.

Genes, Journal Year: 2023, Volume and Issue: 14(5), P. 1060 - 1060

Published: May 9, 2023

Fragile X syndrome is a neuro-developmental disease affecting intellectual abilities and social interactions. Drosophila melanogaster represents consolidated model to study neuronal pathways underlying this syndrome, especially because the recapitulates complex behavioural phenotypes. protein, or FMRP, required for normal structure correct synaptic differentiation in both peripheral central nervous systems, as well connectivity during development of circuits. At molecular level, FMRP has crucial role RNA homeostasis, including transposon regulation gonads D. m. Transposons are repetitive sequences regulated at transcriptional post-transcriptional levels avoid genomic instability. De-regulation transposons brain response chromatin relaxation previously been related neurodegenerative events models. Here, we demonstrate first time that silencing larval adult brains “loss function” dFmr1 mutants. This highlights flies kept isolation, defined asocial conditions, experience activation transposable elements. In all, these results suggest pathogenesis certain neurological alterations abnormal behaviors.

Language: Английский

Citations

1