Biology subjects

Medeiros, A. M.

Publications and source records attributed to Medeiros, A. M..

4 recordsLinked to original sources

bioRxiv2025

Sex-specific control of locomotor behavior by neuronal Arhgef10 in aged Drosophila

Mutations and polymorphisms in the Rho guanine nucleotide exchange factor 10 (ARHGEF10) locus are associated with behavioral and locomotor dysfunctions in humans, including psychiatric disorders and polyneuropathies that show age- and sex-specific prevalence. ARHGEF10 encodes a conserved guanine exchange factor that activates Rho GTPases and has proposed roles in cell migration and adhesion, but the relevant cell types and mechanisms underlying its age- and sex-dependent effects remain unclear. Drosophila darhgef10 gene is the single orthologue of vertebrate ARHGEF10 and its paralogue ARHGEF10L. Here, to gain more direct insight into possible age- and sex-dependent ARHGEF10 neuromuscular functions, we generated darhgef10 knock-out flies and quantified induced walking kinematics with high-speed imaging and coarse spontaneous behaviors--walking, micromovements, rest, and sleep--in open arenas. Mutants of both sexes exhibited abnormal walking kinematics, which worsened with age in females. Cell-type-specific knockdowns indicated that locomotor phenotypes arose primarily from neuronal, rather than glial or muscle, requirements. dArhgef10 was especially critical in glutamatergic motor neurons of aged females. dArhgef10 was also required for wakefulness and activity initiation in females but, surprisingly, not in males. Genetic rescue and isoform expression analyses suggested that sexually-dimorphic expression of long isoforms RC and/or RD underlies at least part of the sex-specific requirements of dArhgef10 in locomotor behavior control, revealing unanticipated complexity in its activity regulation. Collectively, our results suggest ARHGEF10 plays an ancient, conserved role in neurons that promotes proper wakefulness and locomotor activity in an age- and sex-dependent manner.

animal behavior and cognition↗

bioRxiv2025

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↗

bioRxiv2024

Covert muscle activity reveals dynamic freezing states and prepares the animal for action

When an animal detects a threat it must make a split-second choice between fight, flight or freezing (1-3). During freezing, skeletal muscles sustain tension to maintain rigid, sometimes atypical postures, for many minutes at a time (4). Meanwhile the animal must dynamically assess its surroundings to plan future actions and ready its body for movement. The interplay between the neural and somatic systems during freezing remains poorly understood. Here we show that freezing Drosophila melanogaster display a striking novel pattern of leg muscle activation unique to immobility, a rhythmic pulsing in the distal tibia. The muscle, which we show to be a previously undescribed leg accessory heart, displays multiple activity modes and ramps up to movement onset, implying a preparation for movement. The frequency of pulsing is dynamically modulated as the fly integrates external threat or safety cues, and artificially increasing pulse frequency leads to freezing breaks, indicating a causal role in the decision to move. Through the identification of a new Drosophila cardiac organ, this study provides a window into the multiple states which can underlie freezing behaviour, and the physiological changes which the body undergoes to ready the animal to move.

neuroscience↗

bioRxiv2022

Sustained spinal motor activity triggered by direct mechanosensory stimulation in adult Drosophila melanogaster

Most vertebrates and invertebrates such as Drosophila melanogaster are able to move in complex environments due to their ability to integrate sensory information along with motor commands. Mechanosensory structures exist along each leg to assist in motor coordination by transmitting external cues or proprioceptive information to motor centers in the central nervous system. Nevertheless, how different mechanosensory structures engage these locomotor centers and their underlying circuits remains poorly understood. Here, we tested the role of mechanosensory structures in movement initiation by optogenetically stimulating specific classes of leg sensory structures. We found that stimulation of leg Mechanosensory Bristles (MsB) and femoral Chordotonal Organ (ChO) is sufficient to initiate forward movement in immobile animals. While the stimulation of the ChO required brain centers to induce forward movement, unexpectedly, brief stimulation of leg MsB triggered sustained cyclic motor activity dependent only on circuits within the Ventral Nerve Cord (VNC). The duration of the MsB-induced movement was dependent on the number of excited cells and specific to leg afferents, since stimulation of MsB in other segments lead to different motor outcomes. MsB-mediated movement lacked inter and intra-leg coordination, but preserved antagonistic muscle activity within joints. Our data shows that sensory stimulation can act in combination with descending commands in order to elicit a faster response to mechanical stimulation. In addition, it sheds light on the ability of specific sensory circuits to modulate motor control, including initiation of movement, presenting a new system to better understand how different levels of coordination are controlled by VNC and central brain locomotor circuits. Significance StatementSensory feedback is critical to allow smooth and stable locomotion. Proprioceptors interact directly with pre-motor centers optimizing and sustaining coordinated movement. However, initiation of moment is considered to be triggered by higher-order centers in the brain. Here we took advantage of the genetic toolkit provided by the fruit fly Drosophila melanogaster to optogenetically activate different classes of leg sensory cells in immobile animals. We found that leg mechanosensory bristles can specifically trigger sustained leg activity independently of higher-order centers as headless flies could sustain prolonged leg movement upon mechanosensory stimulation. Moreover, while this sensory-evoked movement lacks intra- and inter-leg coordination, it still preserved basic antagonistic muscle activity. These findings suggest a parallel mechanism to trigger fast movement upon sensory stimulation. In addition, it provides a new model for movement initiation and a point-of-entry to define pre-motor circuits.

neuroscience↗