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Gaspar, P.

Publications and source records attributed to Gaspar, P..

8 recordsLinked to original sources

Genetic sex of enteric neurons enables ovarian relaxin togate maternal gut plasticity

Animals must align intestinal plasticity and feeding with reproductive state, yet the checkpoint that gates these adaptations is unknown. Here we show that an ovary-to-enteric-neuron axis gates the onset of maternal gut plasticity in Drosophila. Genetic sex establishes endocrine competence in a subset of enteric neurons via the sex determination pathway, enabling female-specific expression of the relaxin-family receptor Lgr3. After mating, steroid signalling increases Lgr3 receptor expression, priming these neurons for reproductive adaptation. Once oocytes mature fully, follicle cells secrete the relaxin-like hormone dILP8, which activates Lgr3 to trigger gut enlargement and increased feeding. Disrupting the sex determination pathway in enteric neurons, Lgr3, or ovarian dILP8 prevents gut enlargement and reduces feeding. Thus, genetic sex establishes competence, steroid signalling primes it, and ovarian relaxin triggers it, defining a maternal intestinal plasticity checkpoint that ensures gut adaptations initiate only once reproduction is underway and energy demands peak. Our findings delineate an ovary-to-enteric-neuron axis that couples reproductive state to maternal gut plasticity.

physiology↗

Sex-dependent neural plasticity in response to damage

Plasticity of intact adult neural tissue in the vicinity of neural damage serves to restore functionality of circuits. Much remains to be learned about the mechanisms regulating this process and the reported sex differences in recovery outcomes. Here, we present the fly gut and its innervation as a simplified model to address these questions. We show that gut damage caused by ingestion of toxic agents resulted in plasticity of the adult enteric neuronal network, manifested as a Reactive Oxygen Species (ROS)-dependent increase in neural tissue, which was reversible after a recovery period. Interestingly, males did not display neural plasticity, and masculinization of neurons in females suppressed the damage-dependent neural growth. Together, these findings position the fly gut as a system to investigate the cellular, molecular, and sex-specific underpinnings of neural plasticity, with implications for therapeutic advancements in neural circuit recovery. SUMMARY STATEMENTThis study establishes the fly gut as a simple system to explore how adult neural tissues differ between sexes in their capacity for plasticity.

neuroscience↗

Intestinal control of feeding initiation in Drosophila melanogaster

The interplay between feeding and excretion is essential for organismal nutrition and survival, yet their mechanistic coupling remains poorly understood. At the onset of life, feeding must be initiated while developmental waste products - the meconium - need to be eliminated. Using Drosophila as a model system, we explored the in vivo mechanisms coordinating these processes. We developed novel behavioral assays for newly eclosed flies and discovered that, similar to neonatal mammals, Drosophila excrete their meconium shortly after eclosion. Remarkably, feeding initiation occurs only after partial meconium elimination. We identified a cis-regulatory element associated with the apterous gene, which, when disrupted, prevents both meconium excretion and adult feeding initiation. These flies develop hindgut obstruction (ileus), avoid food, and exhibit increased proboscis extension sleep - a behaviour we found plays a functional role in waste clearance under normal conditions. Through experimental inhibition of meconium excretion, we established that this process is prerequisite for feeding initiation, suggesting a gut-to-brain signaling circuit that couples these fundamental physiological processes. The progression of phenotypes we observed parallels the hallmarks of mechanical ileus in humans. Our findings reveal previously unrecognized links between intestinal clearance, feeding behavior, and survival, with potential implications for understanding similar processes across species.

developmental biology↗

Hyperspectral Sensing for High-Throughput Screening of Boron Tolerance in Grapevines

Boron (B) is an essential micronutrient for grapevine growth, yet excessive levels can impair photosynthesis, reduce yields, and diminish fruit quality. In this study, we evaluated the potential of hyperspectral radiometry combined with machine learning to identify B-tolerant rootstocks rapidly and cost-effectively. We screened both commercial grapevine rootstocks and wild Vitis germplasm under B treatments ranging from 0.5 to 8 ppm, measuring leaf B accumulation, stomatal conductance, photosystem II efficiency, and leaf reflectance (R380-R1100 nm). Our results revealed substantial genotypic variation in B exclusion, with some genotypes maintaining low leaf B content despite high external concentrations. Classification models (Partial Least Squares Discriminant Analysis and Random Forest classification) outperformed regression models (Partial Least Squares Regression and Random Forest regression) in distinguishing B-excluding genotypes, achieving moderate to high accuracy within just eight days after stress initiation. Vegetation indices such as Normalized Difference Vegetation Index (NDVI), Photochemical Reflectance Index (PRI), Structure Insensitive Pigment Index (SIPI), and Chlorophyll Index (CI) indicated that B stress reduces chlorophyll levels and may induce carotenoid accumulation, suggesting a photosynthetic tolerance mechanism. Although quantitative prediction of leaf B content proved more challenging, simulations showed that even modest prediction accuracies can substantially boost genetic gains if larger populations are screened, and selection intensities are increased. These findings underscore the value of hyperspectral radiometry for high-throughput phenotyping, allowing breeders to rapidly identify and advance B-tolerant rootstocks.

plant biology↗

Alterations of adult prefrontal circuits induced by early postnatal fluoxetine treatment mediated by 5-HT7 receptors.

The prefrontal cortex (PFC) plays a key role in high-level cognitive functions and emotional behaviors, and PFC alterations correlate with different brain disorders including major depression and anxiety. In mice, the first two postnatal weeks represent a critical period of high sensitivity to environmental changes. In this temporal window, serotonin (5- HT) levels regulate the wiring of PFC cortical neurons. Early life insults and postnatal exposure to the selective serotonin reuptake inhibitor fluoxetine (FLX) affect PFC development leading to depressive and anxiety-like phenotypes in adult mice. However, the mechanisms responsible for these dysfunctions remain obscure. We found that postnatal FLX exposure (PNFLX) results in reduced overall firing, and high-frequency bursting of putative pyramidal neurons (PNs) of deep layers of the medial PFC (mPFC) of adult mice in vivo. Ex-vivo, patch-clamp recordings revealed that PNFLX abolished high-frequency firing in a distinct subpopulation of deep-layer mPFC PNs, which transiently express the serotonin transporter SERT. SERT+ and SERT- PNs exhibit distinct morpho-functional properties. Genetic deletion of 5-HT7Rs prevented the PNFLX-induced reduction of PN firing in vivo and pharmacological 5-HT7R blockade precluded altered firing of SERT+ PNs in vitro. This indicates a pivotal role of this 5-HTR subtype in mediating 5-HT-dependent maturation of PFC circuits that are susceptible to early-life insults. Overall, our results suggest potential novel neurobiological mechanisms, underlying detrimental neurodevelopmental consequences induced by early-life alterations of 5-HT levels.

neuroscience↗

Characterisation of the genetic architecture underlying eye size variation within Drosophila melanogaster and Drosophila simulans

The compound eyes of insects exhibit striking variation in size, reflecting adaptation to different lifestyles and habitats. However, the genetic and developmental bases of variation in insect eye size is poorly understood, which limits our understanding of how these important morphological differences evolve. To address this, we further explored natural variation in eye size within and between four species of the Drosophila melanogaster species subgroup. We found extensive variation in eye size among these species, and flies with larger eyes generally had a shorter inter-ocular distance and vice versa. We then carried out quantitative trait loci (QTL) mapping of intra-specific variation in eye size and inter-ocular distance in both D. melanogaster and D. simulans. This revealed that different genomic regions underlie variation in eye size and inter-ocular distance in both species, which we corroborated by introgression mapping in D. simulans. This suggests that although there is a trade-off between eye size and inter-ocular distance, variation in these two traits is likely to be caused by different genes and so can be genetically decoupled. Finally, although we detected QTL for intra-specific variation in eye size at similar positions in D. melanogaster and D. simulans, we observed differences in eye fate commitment between strains of these two species. This indicates that different developmental mechanisms and therefore, most likely, different genes contribute to eye size variation in these species. Taken together with the results of previous studies, our findings suggest that the gene regulatory network that specifies eye size has evolved at multiple genetic nodes to give rise to natural variation in this trait within and among species.

evolutionary biology↗

tartan underlies the evolution of male genital morphology

Male genital structures are among the most rapidly evolving morphological traits and are often the only features that can distinguish closely related species. This process is thought to be driven by sexual selection and may reinforce species separation. However, while the genetic basis of many phenotypic differences have been identified, we still lack knowledge about the genes underlying evolutionary differences in male genital organs and organ size more generally. The claspers (surstyli) are periphallic structures that play an important role in copulation in insects. Here we show that natural variation in clasper size and bristle number between Drosophila mauritiana and D. simulans is caused by evolutionary changes in tartan (trn), which encodes a transmembrane leucine-rich repeat domain protein that mediates cell-cell interactions and affinity differences. There are no fixed amino acid differences in trn between D. mauritiana and D. simulans but differences in the expression of this gene in developing genitalia suggest cis-regulatory changes in trn underlie the evolution of clasper morphology in these species. Finally, analysis of reciprocal hemizyotes that are genetically identical, except for which species the functional allele of trn is from, determined that the trn allele of D. mauritiana specifies larger claspers with more bristles than the allele of D. simulans. Therefore we have identified the first gene underlying evolutionary change in the size of a male genital organ, which will help to better understand the rapid diversification of these structures and the regulation and evolution of organ size more broadly.\n\nSignificance StatementThe morphology of male genital organs evolves rapidly driven by sexual selection. However, little is known about the genes underlying genitalia differences between species. Identifying these genes is key to understanding how sexual selection acts on development to produce rapid phenotypic change. We have found that the gene tartan underlies differences between male Drosophila mauritiana and D. simulans in the size and bristle number of the claspers - genital projections that grasp the female during copulation. Moreover, since tartan encodes a protein that is involved in cell affinity, this may represent a new developmental mechanism for morphological change. Therefore, our study provides new insights into genetic and developmental bases for the rapid evolution of male genitalia and organ size more generally.

evolutionary biology↗

Early life stress impairs postnatal oligodendrogenesis and adult behavior through activity-dependent mechanisms

Exposure to stress during early life (infancy/childhood) has long-term effects on the structure and function of the prefrontal cortex (PFC) and increases the risk for adult depression and anxiety disorders. However, little is known about the molecular and cellular mechanisms of these effects. Here we focused on changes induced by chronic maternal separation during the first two weeks of postnatal life. Unbiased mRNA expression profiling in the medial PFC (mPFC) of maternally separated (MS) pups identified an increased expression of myelin-related genes and a decreased expression of immediate early genes. Oligodendrocyte lineage markers and birthdating experiments indicated a precocious oligodendrocyte differentiation in the mPFC at P15, leading to a depletion of the oligodendrocyte progenitor pool in MS adults. We tested the role of neuronal activity in oligodendrogenesis, using designed receptors exclusively activated by designed drugs (DREADDs) techniques. hM4Di or hM3Dq constructs were transfected into mPFC neurons using fast-acting AAV8 viruses. Reduction of mPFC neuron excitability during the first two postnatal weeks caused a premature differentiation of oligodendrocytes similar to the MS pups, while chemogenetic activation normalized it in the MS animals. Bidirectional manipulation of neuron excitability in the mPFC during the P2-P14 period had long lasting effects on adult emotional behaviours and on temporal object recognition: hM4Di mimicked MS effects, while hM3Dq prevented the pro-depressive effects and short term memory impairment of MS. Thus, our results identify neuronal activity as a critical target of early life stress and demonstrate its function in controlling both postnatal oligodendrogenesis and adult mPFC-related behaviors.

animal behavior and cognition↗