Drosophila epidermal cells are intrinsically mechanosensitive and drive nociceptive behavioral outputs

Yoshino, Jiro; Mali, Sonali; Williams, Claire; Morita, Takeshi; Emerson, Clifton W.; Arp, Christopher D.; Sophie, Miller; Yin, Chang; The, Lydia; Chikaya, Hemmi; Motoyoshi, Mana; Ishii, Kenichi; Emoto, Kazuo; Bautista, Diana M.; Parrish, Jay Z.

doi:10.1101/2022.10.07.511265

Cited by 3 publications

(3 citation statements)

References 80 publications

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“…, 2018 ; Mikesell et al. , 2022 ; Yoshino et al. , 2022 ): Chemo- or optogenetic activation of keratinocytes promotes sensory afferent firing and nocifensive behaviors, while electrically silencing keratinocytes attenuates these behaviors.…”

Section: Introductionmentioning

confidence: 99%

Sensory axons induce epithelial lipid microdomain remodeling and determine the distribution of junctions in the epidermis

Rosa

Nassman

Sagasti

2023

MBoC

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Epithelial cell properties are determined by the polarized distribution of membrane lipids, the cytoskeleton, and adhesive junctions. Epithelia are often profusely innervated, but little work has addressed how neurites affect epithelial organization. We previously found that basal keratinocytes in the zebrafish epidermis enclose axons in ensheathment channels sealed by autotypic junctions. Here we characterized how axons remodel cell membranes, the cytoskeleton, and junctions in basal keratinocytes. At the apical surface of basal keratinocytes, axons organized lipid microdomains quantitatively enriched in reporters for PI(4,5)P2 and liquid-ordered (Lo) membranes. Lipid microdomains supported the formation of cadherin-enriched F-actin protrusions, which wrapped around axons, likely initiating ensheathment. In the absence of axons, cadherin-enriched microdomains formed on basal cells, but did not organize into contiguous domains. Instead, these isolated domains formed heterotypic junctions with periderm cells, a distinct epithelial cell type. Thus, axon endings dramatically remodel polarized epithelial components and regulate epidermal adhesion. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text]

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Section: Introductionmentioning

confidence: 99%

Sensory axons induce epithelial lipid microdomain remodeling and determine the distribution of junctions in the epidermis

Rosa

Nassman

Sagasti

2023

MBoC

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“…In such a case, nociceptors would exhibit heightened sensitivity to epidermal ion flux, and recent studies indicate that epidermal stimulation influences response properties of SSNs including Drosophila nociceptors (82)(83)(84). However, we found that mutation of the mechanosensory channel gene Piezo decoupled dendrite intercalation and mechanical hypersensitivity.…”

Section: Discussionmentioning

confidence: 53%

Dendrite intercalation between epidermal cells tunes nociceptor sensitivity to mechanical stimuli inDrosophilalarvae

Luedke,

Yoshino,

Yin

et al. 2023

Preprint

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An animal's 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.

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“…Second, epidermal dendrite intercalation could facilitate nociceptor activation through enhanced ionic coupling to epidermal cells, analogous to lateral excitation that improves motion sensitivity of ON bipolar cells [87]. In such a case, nociceptors would exhibit heightened sensitivity to epidermal ion flux, and recent studies indicate that epidermal stimulation influences response properties of SSNs including Drosophila nociceptors [88][89][90]. However, we found that mutation of the mechanosensory channel gene Piezo decoupled dendrite intercalation and mechanical hypersensitivity.…”

Section: Plos Geneticsmentioning

confidence: 76%

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

Luedke,

Yoshino,

Yin

et al. 2024

PLoS Genet

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An animal’s 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.

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Drosophila epidermal cells are intrinsically mechanosensitive and drive nociceptive behavioral outputs

Cited by 3 publications

References 80 publications

Sensory axons induce epithelial lipid microdomain remodeling and determine the distribution of junctions in the epidermis

Sensory axons induce epithelial lipid microdomain remodeling and determine the distribution of junctions in the epidermis

Dendrite intercalation between epidermal cells tunes nociceptor sensitivity to mechanical stimuli inDrosophilalarvae

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

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