Biology subjects

Ghezzi, A.

Publications and source records attributed to Ghezzi, A..

7 recordsLinked to original sources

bioRxiv2025

Peripheral modulation of Pumilio in intestinal stem cells and the corpus allatum affects sleep latency in Drosophila

While central circuits governing sleep are well-studied, the contribution of signaling from peripheral tissues remains a critical yet less understood aspect of sleep regulation. The highly conserved RNA-binding protein Pumilio (Pum) is a post-transcriptional regulator expressed in multiple tissues that influence systemic physiology, but its role in modulating basal sleep has not been established. Although Pumilios function in central neurons has been linked to sleep homeostasis following deprivation, whether it regulates sleep through peripheral mechanisms remains unknown. Here, we use conditional genetic tools in the fruit fly Drosophila melanogaster to demonstrate that Pumilio acts in the intestinal stem cells (ISCs) and the endocrine corpus allatum (CA) to specifically regulate the transition to sleep. Reducing Pumilio function in either the ISCs or the CA independently and significantly accelerates nighttime sleep onset, while overexpression produces the opposite effect. This behavioral change is accompanied by widespread transcriptional alterations in the brain, characterized by a robust upregulation of genes involved in cellular stress responses, including Heat shock protein 83 (Hsp83). Our findings reveal a previously unrecognized gut-endocrine-brain signaling axis and identify peripheral post-transcriptional regulation as a key input to the central control of sleep behavior.

neuroscience↗

bioRxiv2025

Gut microbiota as a modulator of circadian neural development in the honey bee model.

Disruption in gut microbiota during the early postnatal period can disrupt normal neural development and result in long-term behavioral alterations1. Similar to other neural systems, the circadian clock mechanism continues to mature after birth2, yet how microbial disturbances in the early period influence the onset of circadian rhythms and the development of central clock mechanisms remains poorly understood. Here we studied whether early-life gut dysbiosis affects the ontogeny of behavioral circadian rhythms and the maturation of clock neurons using the honey bee (Apis mellifera), a model organism that shares features of postnatal development of behavioral circadian rhythm and clock system3-5 with humans6. Our findings demonstrate that antibiotic-treated and gnotobiotic-reared bees display reduced rhythmicity compared to controls. These treatments also impair the development of the circadian pacemaker, marked by fewer Pigment-Dispersing Factor (PDF)-expressing neurons. Additionally, antibiotic exposure increased the expression of the Insulin-like Growth Factor Binding Protein Acid Labile Subunit (IGFALS) in early ages, which stabilizes the IGF-1/27, a hormone important for neurodevelopmental processes42. Together, these results identify gut microbiota as a modulator of circadian development. Our work provides an understanding of how early-life microbial disruptions influence the development of circadian rhythms, providing information that may extend to other animals, including humans.

neuroscience↗

bioRxiv2024

Alcohol-induced sleep dysregulation in Drosophila is dependent on the neuropeptide PDF

Alcohol exposure is known to trigger homeostatic adaptations in the brain that lead to the development of tolerance and dependence. These adaptations are also believed to be the root of a series of disturbances in sleep patterns that often manifest during the development of alcoholism and can have significant clinical and economic consequences. Unfortunately, the neuronal and genetic pathways that control the effects of alcohol on sleep are currently unknown, thus limiting our efforts to find effective treatment. In this study, we conduct a mechanistic exploration of the relationships between alcohol and sleep alterations using a Drosophila model system. We show that the genetic manipulation of the ventral lateral neurons (LNv) --a set of neurons known to control sleep in Drosophila-- disrupts alcohol sensitivity and tolerance. Moreover, we show that alcohol exposure induces a series of alterations in sleep patterns that last for several days. Our results demonstrate that a single alcohol exposure promotes daytime sleep, alters the structure of sleep during the night, and reduces morning anticipatory behavior. In addition, we show that some of these alterations partially depend on the activity of the neuropeptide PDF, a key element in regulating sleep architecture. We propose that alcohol-induced sleep disruption stems from alterations in the activity of the PDF-releasing LNv neurons and that these alterations are similar to those that produce alcohol tolerance.

neuroscience↗

bioRxiv2022

Defensiveness measurement in honey bees (Apis mellifera)and brain expression of associated genes after noxious stimulus

Honey bee (Apis mellifera sp.) colonies and individuals respond variably to disturbances. In this study, we examined the role of neural modulation and metabolism in constitutive and experience-dependent differences in defensive response. We compared brain gene expression in bees of identified gentle and defensive colonies in a standard assay. For neuromodulation, we examined membrane receptor genes for the biogenic amines dopamine (DOPR2), octopamine (OAR), and serotonin (5HT2a), and the enzyme gene in the synthesis pathway (THR). To examine neural metabolism, we assessed the Oxidative Phosphorylation Pathway "OXPHOS" gene expression (i.e., ND51 and ND20-LIKE). Bees of defensive colonies had a significantly lower expression of amine receptor, synthesis genes, and OXPHOS genes. Experience differences or exposure to nociceptive neurons activated by nocive stimuli (electric shock) led to differences in the expression of all genes except 5HT2a. The same target genes demonstrated an increase in expression levels after electric shock and sting response. We discuss the convergence of neuromodulation, neural metabolism

animal behavior and cognition↗

bioRxiv2022

A butterfly pan-genome reveals a large amount of structural variation underlies the evolution of chromatin accessibility

Despite insertions and deletions being the most common structural variants (SVs) found across genomes, not much is known about how much these SVs vary within populations and between closely related species, nor their significance in evolution. To address these questions, we characterized the evolution of indel SVs using genome assemblies of three closely related Heliconius butterfly species. Over the relatively short evolutionary timescales investigated, up to 18.0% of the genome was composed of indels between two haplotypes of an individual H. charithonia butterfly and up to 62.7% included lineage-specific SVs between the genomes of the most distant species (11 Mya). Lineage-specific sequences were mostly characterized as transposable elements (TEs) inserted at random throughout the genome and their overall distribution was similarly affected by linked selection as single nucleotide substitutions. Using chromatin accessibility profiles (i.e., ATAC-seq) of head tissue in caterpillars to identify sequences with potential cis-regulatory function, we found that out of the 31,066 identified differences in chromatin accessibility between species, 30.4% were within lineage-specific SVs and 9.4% were characterized as TE insertions. These TE insertions were localized closer to gene transcription start sites than expected at random and were enriched for several transcription factor binding site candidates with known function in neuron development in Drosophila. We also identified 24 TE insertions with head-specific chromatin accessibility. Our results show high rates of structural genome evolution that were previously overlooked in comparative genomic studies and suggest a high potential for structural variation to serve as raw material for adaptive evolution.

genomics↗

bioRxiv2019

pumilio regulates sleep homeostasis in response to chronic sleep deprivation in Drosophila melanogaster

Recent studies have identified the Drosophila brain circuits involved in the sleep/wake switch and have pointed to the modulation of neuronal excitability as one of the underlying mechanisms triggering sleep need. In this study we aimed to explore the link between the homeostatic regulation of neuronal excitability and sleep behavior in the circadian circuit. For this purpose, we selected the neuronal homeostasis protein Pumilio (Pum), whose main function is to repress protein translation and has been linked to modulation of neuronal excitability during chronic patterns of altered neuronal activity. Here we explore the effects of Pum on sleep homeostasis in Drosophila melanogaster, which shares most of the major features of mammalian sleep homeostasis. Our evidence indicates that Pum is necessary for sleep rebound and that its effect is more pronounced during chronic sleep deprivation (84 hours) than acute deprivation (12 hours). Knockdown of pum, results in a reduction of sleep rebound during acute sleep deprivation and the complete abolishment of sleep rebound during chronic sleep deprivation. These behavioral changes were associated with accompanying changes in the expression of genes involved in the regulation of neuronal excitability. Interestingly, pum knockdown also increased baseline daytime sleep, suggesting that Pum differentially regulates rebound and normal sleep. Based on these findings, we propose that Pum is a critical regulator of sleep homeostasis through neural adaptations triggered during sleep deprivation and induces rebound sleep by altering neuronal excitability.

neuroscience↗

bioRxiv2017

Electrostatic Tuning of a Potassium Channel in Electric Fish

Molecular and biophysical variation contributes to the evolution of adaptive phenotypes, particularly behavior, though it is often difficult to understand precisely how. The adaptively significant electric organ discharge behavior of weakly electric fish is the direct result of biophysical membrane properties set by ion channels. Here we describe a voltage-gated potassium channel gene in African mormyrid electric fishes, that is under positive selection and highly expressed in the electric organ. The channel produced by this gene shortens electric organ action potentials by activating quickly and at hyperpolarized membrane potentials. Surprisingly, the source of these unique properties is a derived patch of negatively charged amino acids in an extracellular loop near the voltage sensor. Further, we demonstrate that this portion of the channel functions differently in vertebrates than the generally accepted model based on the shaker channel, and suggest a role for this loop in the evolutionary tuning of voltage-dependent channels.

evolutionary biology↗