Biology subjects

Parrish, J. Z.

Publications and source records attributed to Parrish, J. Z..

8 recordsLinked to original sources

bioRxiv2025

Altering cell size asymmetry in Drosophila neural stem cells creates supernumerary stem cells with limited lineage expansion potential

Asymmetrically dividing invertebrate and vertebrate stem cells can generate unequal sized sibling cells. However, the functional implications of cell size asymmetry (CSA) are underexplored. Here, we use Drosophila neural stem cells (NSCs) to investigate how changes in CSA impact NSC proliferation and cell fate decisions. Using live cell imaging, NSC lineage analysis, and gene expression profiling, we find that altering CSA increases the NSC pool but decreases lineage size and the number of differentiating progeny cells. Modeling CSA in silico with a volume-sensitivity and NSC self-inhibition model can recapitulate these findings. Gene expression profiling further revealed that the NSC growth regulator Imp and the G1-S cell cycle regulator CycE are upregulated in NSCs with altered CSA, providing a potential molecular link to the volume-sensitivity model. We propose that cell size and position regulate NSC proliferation and differential potential, impacting lineage progression and progeny cell differentiation in the developing Drosophila brain.

cell biology↗

bioRxiv2025

The engulfment receptor Draper is required for epidermal dendrite ensheathment

Our experience of the external world is shaped by somatosensory neurons (SSNs) that innervate our skin and mediate responses to a range of environmental stimuli. The precise innervation patterns and response properties of SSNs are determined in part by specialized interactions with resident skin cells. One such interaction involves the preferential ensheathment of some SSNs by epidermal cells, an evolutionarily conserved intercellular interaction that regulates SSN morphogenesis and mechanical nociceptive sensitivity in Drosophila. The morphogenetic events during ensheathment resemble phagocytic engulfment, therefore we hypothesized that phagocytic receptors mediate molecular recognition of neurites to induce ensheathment. From a screen of epidermally expressed phagocytic receptors we found that the nimrod receptor gene Draper (Drpr) functions in epidermal cells to promote ensheathment. Endogenous Drpr accumulates at sites of epidermal ensheathment but not at epidermal contact sites with unensheathed neurites. Furthermore, overexpressing Drpr increased ensheathment selectively on neurons that are normally ensheathed, suggesting that molecular recognition by Drpr accounts for the specificity of ensheathment. Indeed, we found that an extracellular reporter for the Drpr ligand Phosphatidylserine (PS) accumulates at sites of ensheathment, and that preventing extracellular PS exposure by overexpressing the PS Flippase ATP8a blocked ensheathment. We additionally found that Orion, which encodes a chemokine-like protein that bridges Drpr-PS interactions, is required for sheath formation. Finally, we found that increasing ensheathment by overexpressing Drpr enhanced nociceptor sensitivity to mechanical stimulus. Altogether, these studies show that Drpr acts in epidermal cells to mediate molecular recognition events that drive ensheathment of neurites marked by extracellular PS.

neuroscience↗

bioRxiv2025

Heat-off responses of epidermal cells sensitize Drosophila larvae to noxious inputs

Perception of external thermal stimuli is critical to animal survival, and although an animals skin is the largest contact surface for thermal inputs, contributions of skin cells to noxious temperature sensing have not been extensively explored. Here, we show that exposure to heat transiently sensitizes Drosophila larvae to subsequent noxious stimuli. This sensitization is induced by prior stimulation of epidermal cells but not nociceptors, suggesting that epidermal cells modulate nociceptor function in response to heat exposure. Indeed, we found that Drosophila epidermal cells are intrinsically thermosensitive, exhibiting robust heat-off responses following warming to noxious temperatures as well as responses to cooling below comfortable temperatures. Further, we found that epidermal heat-off calcium responses involve influx of extracellular calcium and require the store-operated calcium channel Orai and its activator Stim. Finally, epidermal heat-off responses and heat-evoked nociceptive sensitization exhibit similar temperature dependencies, and we found that Stim and Orai are required in epidermal cells for heat-evoked nociceptive sensitization. Hence, epidermal thermosensory responses provide a form of adaptive sensitization to facilitate noxious heat avoidance.

neuroscience↗

bioRxiv2024

Axon length-dependent synapse loss is mediated by neuronal cytokine-induced glial phagocytosis

Many neurodegenerative disorders (NDDs) preferentially affect neurons with long or complex axonal arbors, but our understanding of this specific vulnerability is limited. Using Drosophila larval class IV dendrite arborization (C4da) neurons, we found that neuronal activation of the integrated stress response (ISR) induces axon length-dependent degeneration (LDD). We identified the Interleukin-6 homologue unpaired 3 (upd3) as both necessary and sufficient for LDD in C4da neurons. Upd3 recruits glial cells to phagocytose presynapses preferentially on neurons with long axons, revealing an intrinsic axon length-dependent vulnerability to glia-mediated presynapse removal. Finally, we found that axon length-dependent presynapse loss in fly models of human NDDs utilized this pathway. Altogether, our studies identify inflammatory cytokine signaling from neurons to glia as a key determinant in axon length-dependent vulnerability. One-Sentence SummarySensory neurons exhibit intrinsic length-dependent vulnerability to presynapse removal driven by cytokine activation of glia.

neuroscience↗

bioRxiv2023

Dendrite intercalation between epidermal cells tunes nociceptor sensitivity to mechanical stimuli in Drosophila larvae

An animals skin provides a first point of contact with the sensory environment, including noxious cues that elicit protective behavioral responses. Nociceptive somatosensory neurons densely innervate and intimately interact with epidermal cells to receive these cues, however the mechanisms by which epidermal interactions shape processing of noxious inputs is still poorly understood. Here, we identify a role for dendrite intercalation between epidermal cells in tuning sensitivity of Drosophila larvae to noxious mechanical stimuli. In wild-type larvae, dendrites of nociceptive class IV da neurons intercalate between epidermal cells at apodemes, which function as body wall muscle attachment sites, but not at other sites in the epidermis. From a genetic screen we identified miR-14 as a regulator of dendrite positioning in the epidermis: miR-14 is expressed broadly in the epidermis but not in apodemes, and miR-14 inactivation leads to excessive apical dendrite intercalation between epidermal cells. We found that miR- 14 regulates expression and distribution of the epidermal Innexins ogre and Inx2 and that these epidermal gap junction proteins restrict epidermal dendrite intercalation. Finally, we found that altering the extent of epidermal dendrite intercalation had corresponding effects on nociception: increasing epidermal intercalation sensitized larvae to noxious mechanical inputs and increased mechanically evoked calcium responses in nociceptive neurons, whereas reducing epidermal dendrite intercalation had the opposite effects. Altogether, these studies identify epidermal dendrite intercalation as a mechanism for mechanical coupling of nociceptive neurons to the epidermis, with nociceptive sensitivity tuned by the extent of intercalation. Author SummaryOur skin provides a first point of contact for a variety of sensory inputs, including noxious cues that elicit pain. Although specialized interactions between skin cells and sensory neurons are known to shape responses to a variety of mechanosensory stimuli including gentle touch and vibration, interactions with skin cells that shape responses to painful mechanical inputs are less well defined. Using the fruit fly Drosophila melanogaster as a model system, we demonstrate that the pattern of epidermal innervation, specifically the extent of dendrite intercalation between epidermal cells, tunes the animals sensitivity to noxious mechanical stimuli. Similar mechanisms may regulate sensitivity to painful mechanical inputs in both pathological and physiological states in vertebrates.

neuroscience↗

bioRxiv2023

A cell atlas of the larval Aedes aegypti ventral nerve cord

Mosquito-borne diseases account for nearly one million human deaths annually, yet we have a limited understanding of developmental events that influence host-seeking behavior and pathogen transmission in mosquitoes. Mosquito-borne pathogens are transmitted during blood meals, hence adult mosquito behavior and physiology have been intensely studied. However, events during larval development shape adult traits, larvae respond to many of the same sensory cues as adults, and larvae are susceptible to infection by many of the same disease-causing agents as adults. Hence, a better understanding of larval physiology will directly inform our understanding of physiological processes in adults. Here, we use single cell RNA sequencing (scRNA-seq) to provide a comprehensive view of cellular composition in the Aedes aegypti larval ventral nerve cord (VNC), a central hub of sensory inputs and motor outputs which additionally controls multiple aspects of larval physiology. We identify more than 35 VNC cell types defined in part by neurotransmitter and neuropeptide expression. We also explore diversity among monoaminergic and peptidergic neurons that likely control key elements of larval physiology and developmental timing, and identify neuroblasts and immature neurons, providing a view of neuronal differentiation in the VNC. Finally, we find that larval cell composition, number, and position are preserved in the adult abdominal VNC, suggesting studies of larval VNC form and function will likely directly inform our understanding adult mosquito physiology. Altogether, these studies provide a framework for targeted analysis of VNC development and neuronal function in Aedes larvae.

neuroscience↗

bioRxiv2022

Drosophila epidermal cells are intrinsically mechanosensitive and drive nociceptive behavioral outputs

Somatosensory neurons (SSNs) that detect and transduce mechanical, thermal, and chemical stimuli densely innervate an animals skin. However, although epidermal cells provide the first point of contact for sensory stimuli. our understanding of roles that epidermal cells play in SSN function, particularly nociception, remains limited. Here, we show that stimulating Drosophila epidermal cells elicits activation of SSNs including nociceptors and triggers a variety of behavior outputs, including avoidance and escape. Further, we find that epidermal cells are intrinsically mechanosensitive and that epidermal mechanically evoked calcium responses require the store-operated calcium channel Orai. Epidermal cell stimulation augments larval responses to acute nociceptive stimuli and promotes prolonged hypersensitivity to subsequent mechanical stimuli. Hence, epidermal cells are key determinants of nociceptive sensitivity and sensitization, acting as primary sensors of noxious stimuli that tune nociceptor output and drive protective behaviors.

neuroscience↗

bioRxiv2018

Microtubule acetylation is required for mechanosensation in Drosophila

At the cellular level, -tubulin acetylation alters the structure of microtubules to render them mechanically resistant to compressive forces. How this biochemical property of microtubule acetylation relates to mechanosensation remains unknown, though prior studies have shown that microtubule acetylation plays a role in touch perception. Here, we identify the major Drosophila -tubulin acetylase (dTAT) and show that it plays key roles in several forms of mechanosensation while exerting little effect on other sensory modalities. dTAT is highly expressed in neurons of the larval peripheral nervous system (PNS), but is not required for normal neuronal morphogenesis. We show that mutation of the acetylase gene or the K40 acetylation site in -tubulin impairs mechanical sensitivity in sensory neurons and behavioral responses to gentle touch, harsh touch, gravity, and sound stimulus, but not thermal stimulus. Finally, we show that dTAT is required for mechanically-induced activation of NOMPC, a microtubule-associated transient receptor potential channel, and functions to maintain integrity of the microtubule cytoskeleton in response to mechanical stimulation.

cell biology↗