{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:24:41Z","timestamp":1790745881065,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.pgen.1011237","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T00:00:00Z","timestamp":1715040000000}}],"reference-count":108,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T00:00:00Z","timestamp":1714003200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NINDS R01 NS076614 and NINDS R21NS125795"],"award-info":[{"award-number":["NINDS R01 NS076614 and NINDS R21NS125795"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32 GM007108-40"],"award-info":[{"award-number":["T32 GM007108-40"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Weill Neurohub","award":["Next Great Ideas Program"],"award-info":[{"award-number":["Next Great Ideas Program"]}]},{"DOI":"10.13039\/100010344","name":"Scan|Design Foundation by Inger and Jens Bruun","doi-asserted-by":"publisher","award":["Innovative Pain Research Grant"],"award-info":[{"award-number":["Innovative Pain Research Grant"]}],"id":[{"id":"10.13039\/100010344","id-type":"DOI","asserted-by":"publisher"}]},{"name":"JSPS"},{"name":"UW"},{"name":"UW Dept. of Biology","award":["Robin M. Harris award and WRF-Hall awar"],"award-info":[{"award-number":["Robin M. Harris award and WRF-Hall awar"]}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>An animal\u2019s 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 <jats:italic>Drosophila<\/jats:italic> 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 <jats:italic>miR-14<\/jats:italic> as a regulator of dendrite positioning in the epidermis: <jats:italic>miR-14<\/jats:italic> is expressed broadly in the epidermis but not in apodemes, and <jats:italic>miR-14<\/jats:italic> inactivation leads to excessive apical dendrite intercalation between epidermal cells. We found that <jats:italic>miR-14<\/jats:italic> 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.<\/jats:p>","DOI":"10.1371\/journal.pgen.1011237","type":"journal-article","created":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T17:52:48Z","timestamp":1714067568000},"page":"e1011237","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Dendrite intercalation between epidermal cells tunes nociceptor sensitivity to mechanical stimuli in Drosophila larvae"],"prefix":"10.1371","volume":"20","author":[{"given":"Kory P.","family":"Luedke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9761-4882","authenticated-orcid":true,"given":"Jiro","family":"Yoshino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica M.","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6920-9935","authenticated-orcid":true,"given":"Kevin","family":"Huynh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0656-9148","authenticated-orcid":true,"given":"Jay Z.","family":"Parrish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,4,25]]},"reference":[{"key":"pgen.1011237.ref001","unstructured":"Institute of Medicine (US) Committee on Advancing Pain Research, Care, and Education. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research [Internet]. Washington (DC): National Academies Press (US); 2011 [cited 2016 Sep 21]. (The National Academies Collection: Reports funded by National Institutes of Health). Available from: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK91497\/"},{"issue":"5","key":"pgen.1011237.ref002","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.tins.2020.03.004","article-title":"Getting in Touch with Mechanical Pain Mechanisms","volume":"43","author":"RZ Hill","year":"2020","journal-title":"Trends Neurosci"},{"issue":"3","key":"pgen.1011237.ref003","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.jpain.2008.09.010","article-title":"Individual differences in pain sensitivity: measurement, causation, and consequences","volume":"10","author":"CS Nielsen","year":"2009","journal-title":"J Pain"},{"key":"pgen.1011237.ref004","doi-asserted-by":"crossref","first-page":"680345","DOI":"10.3389\/fncel.2021.680345","article-title":"Transparent Touch: Insights From Model Systems on Epidermal Control of Somatosensory Innervation","volume":"15","author":"C Yin","year":"2021","journal-title":"Front Cell Neurosci"},{"key":"pgen.1011237.ref005","first-page":"8","article-title":"A conserved morphogenetic mechanism for epidermal ensheathment of nociceptive sensory neurites","volume":"11","author":"N Jiang","year":"2019","journal-title":"Elife"},{"issue":"2","key":"pgen.1011237.ref006","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1042\/bj20031089","article-title":"Ca2+ waves in keratinocytes are transmitted to sensory neurons: the involvement of extracellular ATP and P2Y2 receptor activation","volume":"380","author":"S Koizumi","year":"2004","journal-title":"Biochem J"},{"issue":"10","key":"pgen.1011237.ref007","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.cub.2009.03.062","article-title":"Cytokine signaling mediates UV-induced nociceptive sensitization in Drosophila larvae","volume":"19","author":"DT Babcock","year":"2009","journal-title":"Curr Biol"},{"issue":"6","key":"pgen.1011237.ref008","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1007\/s00424-009-0703-x","article-title":"TRPV3 in keratinocytes transmits temperature information to sensory neurons via ATP","volume":"458","author":"S Mandadi","year":"2009","journal-title":"Pflugers Arch"},{"issue":"5714","key":"pgen.1011237.ref009","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1126\/science.1108609","article-title":"Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin","volume":"307","author":"A Moqrich","year":"2005","journal-title":"Science"},{"issue":"2","key":"pgen.1011237.ref010","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41422-018-0129-0","article-title":"STIM1 thermosensitivity defines the optimal preference temperature for warm sensation in mice","volume":"29","author":"X Liu","year":"2019","journal-title":"Cell Res"},{"issue":"34","key":"pgen.1011237.ref011","doi-asserted-by":"crossref","first-page":"E3225","DOI":"10.1073\/pnas.1312933110","article-title":"UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling","volume":"110","author":"C Moore","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pgen.1011237.ref012","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.pain.2008.03.016","article-title":"Voltage-gated sodium channel expression in rat and human epidermal keratinocytes: evidence for a role in pain","volume":"139","author":"P Zhao","year":"2008","journal-title":"Pain"},{"issue":"1","key":"pgen.1011237.ref013","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/nn.3881","article-title":"Unbiased classification of sensory neuron types by large-scale single-cell RNA sequencing","volume":"18","author":"D Usoskin","year":"2015","journal-title":"Nat Neurosci"},{"issue":"9","key":"pgen.1011237.ref014","doi-asserted-by":"crossref","first-page":"e0185543","DOI":"10.1371\/journal.pone.0185543","article-title":"Diversity amongst trigeminal neurons revealed by high throughput single cell sequencing","volume":"12","author":"MQ Nguyen","year":"2017","journal-title":"PLoS ONE"},{"issue":"7790","key":"pgen.1011237.ref015","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/s41586-019-1900-1","article-title":"The emergence of transcriptional identity in somatosensory neurons","volume":"577","author":"N Sharma","year":"2020","journal-title":"Nature"},{"issue":"3","key":"pgen.1011237.ref016","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.cels.2016.08.010","article-title":"Single-Cell Transcriptomics Reveals that Differentiation and Spatial Signatures Shape Epidermal and Hair Follicle Heterogeneity","volume":"3","author":"S Joost","year":"2016","journal-title":"Cell Syst"},{"issue":"4","key":"pgen.1011237.ref017","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.celrep.2018.09.006","article-title":"Transcriptional Programming of Normal and Inflamed Human Epidermis at Single-Cell Resolution","volume":"25","author":"JB Cheng","year":"2018","journal-title":"Cell Rep"},{"issue":"4","key":"pgen.1011237.ref018","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.jid.2018.01.016","article-title":"Spatial and Single-Cell Transcriptional Profiling Identifies Functionally Distinct Human Dermal Fibroblast Subpopulations","volume":"138","author":"C Philippeos","year":"2018","journal-title":"J Invest Dermatol"},{"issue":"2","key":"pgen.1011237.ref019","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/j.1346-8138.2001.tb00091.x","article-title":"Distribution density of intraepidermal nerve fibers in normal human skin","volume":"28","author":"T Kawakami","year":"2001","journal-title":"J Dermatol"},{"issue":"10","key":"pgen.1011237.ref020","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1179\/1743132814Y.0000000377","article-title":"Intraepidermal nerve fiber density of healthy human","volume":"36","author":"Y Liu","year":"2014","journal-title":"Neurol Res"},{"issue":"24","key":"pgen.1011237.ref021","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1016\/j.cub.2007.11.029","article-title":"Nociceptive neurons protect Drosophila larvae from parasitoid wasps","volume":"17","author":"RY Hwang","year":"2007","journal-title":"Curr Biol"},{"issue":"3","key":"pgen.1011237.ref022","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1242\/dev.110.3.791","article-title":"The embryonic development of larval muscles in Drosophila","volume":"110","author":"M. Bate","year":"1990","journal-title":"Development"},{"issue":"1","key":"pgen.1011237.ref023","first-page":"189","article-title":"Muscle development and attachment to the epidermis is accompanied by expression of beta 3 and beta 1 tubulin isotypes, respectively","volume":"40","author":"D Buttgereit","year":"1996","journal-title":"Int J Dev Biol"},{"issue":"11","key":"pgen.1011237.ref024","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1101\/gad.259119.115","article-title":"The SLC36 transporter Pathetic is required for extreme dendrite growth in Drosophila sensory neurons","volume":"29","author":"WY Lin","year":"2015","journal-title":"Genes Dev"},{"issue":"6818","key":"pgen.1011237.ref025","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/35053110","article-title":"Role for a bidentate ribonuclease in the initiation step of RNA interference","volume":"409","author":"E Bernstein","year":"2001","journal-title":"Nature"},{"issue":"5538","key":"pgen.1011237.ref026","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1126\/science.1062039","article-title":"A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans","volume":"293","author":"SW Knight","year":"2001","journal-title":"Science (New York, NY)"},{"issue":"6","key":"pgen.1011237.ref027","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/j.neuron.2009.08.006","article-title":"The microRNA bantam functions in epithelial cells to regulate scaling growth of dendrite arbors in drosophila sensory neurons","volume":"63","author":"JZ Parrish","year":"2009","journal-title":"Neuron"},{"issue":"1","key":"pgen.1011237.ref028","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1242\/dev.113423","article-title":"Coordinate control of terminal dendrite patterning and dynamics by the membrane protein Raw","volume":"142","author":"J Lee","year":"2015","journal-title":"Development"},{"issue":"2","key":"pgen.1011237.ref029","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1083\/jcb.143.2.501","article-title":"Visualization of phosphoinositides that bind pleckstrin homology domains: calcium- and agonist-induced dynamic changes and relationship to myo-[3H]inositol-labeled phosphoinositide pools","volume":"143","author":"P V\u00e1rnai","year":"1998","journal-title":"J Cell Biol"},{"issue":"1","key":"pgen.1011237.ref030","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.neuron.2011.10.036","article-title":"Integrins regulate repulsion-mediated dendritic patterning of drosophila sensory neurons by restricting dendrites in a 2D space","volume":"73","author":"C Han","year":"2012","journal-title":"Neuron"},{"issue":"1","key":"pgen.1011237.ref031","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.neuron.2011.10.033","article-title":"Integrins establish dendrite-substrate relationships that promote dendritic self-avoidance and patterning in drosophila sensory neurons","volume":"73","author":"ME Kim","year":"2012","journal-title":"Neuron"},{"issue":"13","key":"pgen.1011237.ref032","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1242\/dev.107573","article-title":"The microRNA bantam regulates a developmental transition in epithelial cells that restricts sensory dendrite growth","volume":"141","author":"N Jiang","year":"2014","journal-title":"Development"},{"issue":"26","key":"pgen.1011237.ref033","doi-asserted-by":"crossref","first-page":"15050","DOI":"10.1073\/pnas.261408198","article-title":"A protein trap strategy to detect GFP-tagged proteins expressed from their endogenous loci in Drosophila","volume":"98","author":"X Morin","year":"2001","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"24","key":"pgen.1011237.ref034","doi-asserted-by":"crossref","first-page":"2748","DOI":"10.1101\/gad.1995910","article-title":"Drosophila miR-14 regulates insulin production and metabolism through its target, sugarbabe","volume":"24","author":"J Varghese","year":"2010","journal-title":"Genes Dev"},{"issue":"3","key":"pgen.1011237.ref035","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S0896-6273(00)80701-1","article-title":"Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis","volume":"22","author":"T Lee","year":"1999","journal-title":"Neuron"},{"issue":"6956","key":"pgen.1011237.ref036","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature01957","article-title":"The nuclear RNase III Drosha initiates microRNA processing","volume":"425","author":"Y Lee","year":"2003","journal-title":"Nature"},{"issue":"9","key":"pgen.1011237.ref037","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/nmeth1079","article-title":"MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells","volume":"4","author":"MS Ebert","year":"2007","journal-title":"Nat Methods"},{"key":"pgen.1011237.ref038","article-title":"A transgenic resource for conditional competitive inhibition of conserved Drosophila microRNAs","author":"TA Fulga","year":"2015","journal-title":"Nat Commun"},{"issue":"15","key":"pgen.1011237.ref039","doi-asserted-by":"crossref","first-page":"2821","DOI":"10.1242\/dev.079939","article-title":"A genome-wide transgenic resource for conditional expression of Drosophila microRNAs","volume":"139","author":"F Bejarano","year":"2012","journal-title":"Development (Cambridge, England)"},{"issue":"17","key":"pgen.1011237.ref040","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1242\/dev.047498","article-title":"Connecting muscles to tendons: tendons and musculoskeletal development in flies and vertebrates","volume":"137","author":"R Schweitzer","year":"2010","journal-title":"Development"},{"issue":"5","key":"pgen.1011237.ref041","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.cub.2009.12.057","article-title":"Pickpocket is a DEG\/ENaC protein required for mechanical nociception in Drosophila larvae","volume":"20","author":"L Zhong","year":"2010","journal-title":"Curr Biol"},{"issue":"7431","key":"pgen.1011237.ref042","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nature11685","article-title":"Drosophila NOMPC is a mechanotransduction channel subunit for gentle-touch sensation","volume":"493","author":"Z Yan","year":"2013","journal-title":"Nature"},{"issue":"33","key":"pgen.1011237.ref043","doi-asserted-by":"crossref","first-page":"13612","DOI":"10.1073\/pnas.1312477110","article-title":"Sound response mediated by the TRP channels NOMPC, NANCHUNG, and INACTIVE in chordotonal organs of Drosophila larvae","volume":"110","author":"W Zhang","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"issue":"2","key":"pgen.1011237.ref044","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S0092-8674(03)00272-1","article-title":"painless, a Drosophila gene essential for nociception","volume":"113","author":"WD Jr Tracey","year":"2003","journal-title":"Cell"},{"issue":"10","key":"pgen.1011237.ref045","doi-asserted-by":"crossref","first-page":"e0186888","DOI":"10.1371\/journal.pone.0186888","article-title":"TrpA1 activation in peripheral sensory neurons underlies the ionic basis of pain hypersensitivity in response to vinca alkaloids","volume":"12","author":"N Boiko","year":"2017","journal-title":"PLoS ONE"},{"issue":"12","key":"pgen.1011237.ref046","doi-asserted-by":"crossref","first-page":"e2113645119","DOI":"10.1073\/pnas.2113645119","article-title":"Nociception and hypersensitivity involve distinct neurons and molecular transducers in Drosophila","volume":"119","author":"P Gu","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pgen.1011237.ref047","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1186\/gb-2003-5-1-r1","article-title":"MicroRNA targets in Drosophila","volume":"5","author":"AJ Enright","year":"2003","journal-title":"Genome Biol"},{"issue":"3","key":"pgen.1011237.ref048","doi-asserted-by":"crossref","first-page":"E60","DOI":"10.1371\/journal.pbio.0000060","article-title":"Identification of Drosophila MicroRNA targets","volume":"1","author":"A Stark","year":"2003","journal-title":"PLoS Biol"},{"issue":"7","key":"pgen.1011237.ref049","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1091\/mbc.11.7.2459","article-title":"Two Drosophila innexins are expressed in overlapping domains and cooperate to form gap-junction channels","volume":"11","author":"LA Stebbings","year":"2000","journal-title":"Mol Biol Cell"},{"issue":"17","key":"pgen.1011237.ref050","first-page":"3823","article-title":"Innexins Ogre and Inx2 are required in glial cells for normal postembryonic development of the Drosophila central nervous system","volume":"126","author":"CE Holcroft","year":"2013","journal-title":"J Cell Sci"},{"issue":"13","key":"pgen.1011237.ref051","doi-asserted-by":"crossref","first-page":"2260","DOI":"10.1523\/JNEUROSCI.1323-22.2023","article-title":"Innexin-Mediated Adhesion between Glia Is Required for Axon Ensheathment in the Peripheral Nervous System","volume":"43","author":"M Das","year":"2023","journal-title":"J Neurosci"},{"issue":"4","key":"pgen.1011237.ref052","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1091\/mbc.e05-11-1059","article-title":"Heteromerization of innexin gap junction proteins regulates epithelial tissue organization in Drosophila","volume":"17","author":"C Lehmann","year":"2006","journal-title":"Mol Biol Cell"},{"issue":"1","key":"pgen.1011237.ref053","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.jinsphys.2017.07.010","article-title":"Live imaging using a FRET glucose sensor reveals glucose delivery to all cell types in the Drosophila brain","volume":"106","author":"A Volkenhoff","year":"2018","journal-title":"J Insect Physiol"},{"issue":"4","key":"pgen.1011237.ref054","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1093\/genetics\/103.4.617","article-title":"Vital Genes That Flank Sex-Lethal, an X-Linked Sex-Determining Gene of DROSOPHILA MELANOGASTER","volume":"103","author":"JA Nicklas","year":"1983","journal-title":"Genetics"},{"issue":"1","key":"pgen.1011237.ref055","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1093\/embo-reports\/kvf012","article-title":"Mapping and identification of essential gene functions on the X chromosome of Drosophila","volume":"3","author":"A Peter","year":"2002","journal-title":"EMBO Rep"},{"issue":"6","key":"pgen.1011237.ref056","doi-asserted-by":"crossref","first-page":"2992","DOI":"10.1091\/mbc.e04-01-0056","article-title":"Gap junction channel protein innexin 2 is essential for epithelial morphogenesis in the Drosophila embryo","volume":"15","author":"R Bauer","year":"2004","journal-title":"Mol Biol Cell"},{"issue":"4","key":"pgen.1011237.ref057","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1021\/acschembio.6b00883","article-title":"The GCaMP-R Family of Genetically Encoded Ratiometric Calcium Indicators","volume":"12","author":"JH Cho","year":"2017","journal-title":"ACS Chem Biol"},{"issue":"4","key":"pgen.1011237.ref058","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.devcel.2010.02.010","article-title":"Dendrite reshaping of adult Drosophila sensory neurons requires matrix metalloproteinase-mediated modification of the basement membranes","volume":"18","author":"K ichiro Yasunaga","year":"2010","journal-title":"Dev Cell"},{"issue":"7","key":"pgen.1011237.ref059","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1242\/dev.120.7.1747","article-title":"Tiggrin, a novel Drosophila extracellular matrix protein that functions as a ligand for Drosophila alpha PS2 beta PS integrins","volume":"120","author":"FJ Fogerty","year":"1994","journal-title":"Development"},{"issue":"6","key":"pgen.1011237.ref060","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a013656","article-title":"Diversification and specialization of touch receptors in skin","volume":"4","author":"DM Owens","year":"2014","journal-title":"Cold Spring Harb Perspect Med"},{"issue":"5","key":"pgen.1011237.ref061","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/1523-1747.ep12550322","article-title":"The specialized junctions between Merkel cell and neurite: an electron microscopic study","volume":"73","author":"M Mihara","year":"1979","journal-title":"J Invest Dermatol"},{"issue":"7502","key":"pgen.1011237.ref062","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/nature13250","article-title":"Epidermal Merkel cells are mechanosensory cells that tune mammalian touch receptors","volume":"509","author":"S Maksimovic","year":"2014","journal-title":"Nature"},{"issue":"6","key":"pgen.1011237.ref063","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/j.neuron.2018.10.034","article-title":"Merkel Cells Activate Sensory Neural Pathways through Adrenergic Synapses","volume":"100","author":"BU Hoffman","year":"2018","journal-title":"Neuron"},{"issue":"9","key":"pgen.1011237.ref064","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/s41583-021-00489-x","article-title":"The mechanosensory neurons of touch and their mechanisms of activation","volume":"22","author":"A Handler","year":"2021","journal-title":"Nat Rev Neurosci"},{"issue":"4","key":"pgen.1011237.ref065","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/s41556-023-01110-2","article-title":"Co-option of epidermal cells enables touch sensing","volume":"25","author":"F Mangione","year":"2023","journal-title":"Nat Cell Biol"},{"issue":"2","key":"pgen.1011237.ref066","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1113\/jphysiol.1966.sp007827","article-title":"Mechanical transmission in a Pacinian corpuscle. An analysis and a theory","volume":"182","author":"WR Loewenstein","year":"1966","journal-title":"J Physiol (Lond)"},{"issue":"6497","key":"pgen.1011237.ref067","doi-asserted-by":"crossref","DOI":"10.1126\/science.abb2751","article-title":"Meissner corpuscles and their spatially intermingled afferents underlie gentle touch perception","volume":"368","author":"NL Neubarth","year":"2020","journal-title":"Science"},{"issue":"3","key":"pgen.1011237.ref068","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/ng1744","article-title":"Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs","volume":"38","author":"R Yi","year":"2006","journal-title":"Nat Genet"},{"issue":"2","key":"pgen.1011237.ref069","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1073\/pnas.0810766105","article-title":"DGCR8-dependent microRNA biogenesis is essential for skin development","volume":"106","author":"R Yi","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"pgen.1011237.ref070","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1016\/j.celrep.2014.05.025","article-title":"A rapid genome-wide microRNA screen identifies miR-14 as a modulator of Hedgehog signaling","volume":"7","author":"K Kim","year":"2014","journal-title":"Cell Rep"},{"issue":"3","key":"pgen.1011237.ref071","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.molcel.2014.09.011","article-title":"miR-14 regulates autophagy during developmental cell death by targeting ip3-kinase 2","volume":"56","author":"C Nelson","year":"2014","journal-title":"Mol Cell"},{"issue":"18","key":"pgen.1011237.ref072","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1101\/gad.439807","article-title":"microRNA miR-14 acts to modulate a positive autoregulatory loop controlling steroid hormone signaling in Drosophila","volume":"21","author":"J Varghese","year":"2007","journal-title":"Genes Dev"},{"issue":"18","key":"pgen.1011237.ref073","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1016\/j.cub.2011.08.020","article-title":"Hedgehog signaling regulates nociceptive sensitization","volume":"21","author":"DT Babcock","year":"2011","journal-title":"Curr Biol"},{"issue":"5","key":"pgen.1011237.ref074","article-title":"Drosophila Insulin receptor regulates the persistence of injury-induced nociceptive sensitization","volume":"11","author":"SH Im","year":"2018","journal-title":"Dis Model Mech"},{"issue":"9","key":"pgen.1011237.ref075","doi-asserted-by":"crossref","DOI":"10.1093\/g3journal\/jkab215","article-title":"\u03b2PS-Integrin acts downstream of Innexin 2 in modulating stretched cell morphogenesis in the Drosophila ovary","volume":"11","author":"YC Huang","year":"2021","journal-title":"G3 (Bethesda)"},{"issue":"1\u20132","key":"pgen.1011237.ref076","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1080\/15419060600631839","article-title":"DE-cadherin, a core component of the adherens junction complex modifies subcellular localization of the Drosophila gap junction protein innexin2","volume":"13","author":"R Bauer","year":"2006","journal-title":"Cell Commun Adhes"},{"issue":"10","key":"pgen.1011237.ref077","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1002\/glia.22541","article-title":"Communication between neuronal somata and satellite glial cells in sensory ganglia","volume":"61","author":"LYM Huang","year":"2013","journal-title":"Glia"},{"issue":"5","key":"pgen.1011237.ref078","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/j.neuron.2016.07.044","article-title":"Coupled Activation of Primary Sensory Neurons Contributes to Chronic Pain","volume":"91","author":"YS Kim","year":"2016","journal-title":"Neuron"},{"issue":"1","key":"pgen.1011237.ref079","first-page":"152","article-title":"Differential expression of the gap junction proteins connexin45, -43, -40, -31, and -26 in mouse skin","volume":"65","author":"A Butterweck","year":"1994","journal-title":"Eur J Cell Biol"},{"issue":"1","key":"pgen.1011237.ref080","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/aja.1002000102","article-title":"Expression of gap junction proteins Cx26, Cx31.1, Cx37, and Cx43 in developing and mature rat epidermis","volume":"200","author":"JA Goliger","year":"1994","journal-title":"Dev Dyn"},{"issue":"5","key":"pgen.1011237.ref081","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1016\/j.bbamem.2008.01.016","article-title":"Regulation of connexons composed of human connexin26 (hCx26) by temperature","volume":"1778","author":"M Steffens","year":"2008","journal-title":"Biochim Biophys Acta"},{"issue":"Pt 19","key":"pgen.1011237.ref082","first-page":"4159","article-title":"Mechanosensitive ATP release from hemichannels and Ca2+ influx through TRPC6 accelerate wound closure in keratinocytes","volume":"127","author":"H Takada","year":"2014","journal-title":"J Cell Sci"},{"issue":"2","key":"pgen.1011237.ref083","doi-asserted-by":"crossref","first-page":"e56744","DOI":"10.1371\/journal.pone.0056744","article-title":"Air-stimulated ATP release from keratinocytes occurs through connexin hemichannels","volume":"8","author":"TP Barr","year":"2013","journal-title":"PLoS ONE"},{"key":"pgen.1011237.ref084","first-page":"7","article-title":"Keratinocytes mediate innocuous and noxious touch via ATP-P2X4 signaling","volume":"16","author":"F Moehring","year":"2018","journal-title":"Elife"},{"key":"pgen.1011237.ref085","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.semcdb.2015.11.018","article-title":"Connexin channels in congenital skin disorders","volume":"50","author":"E Lilly","year":"2016","journal-title":"Semin Cell Dev Biol"},{"issue":"1","key":"pgen.1011237.ref086","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/jcp.20647","article-title":"Possible involvement of gap junctions in the barrier function of tight junctions of brain and lung endothelial cells","volume":"208","author":"K Nagasawa","year":"2006","journal-title":"J Cell Physiol"},{"issue":"2","key":"pgen.1011237.ref087","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.neuron.2016.03.012","article-title":"Nonlinear Spatiotemporal Integration by Electrical and Chemical Synapses in the Retina","volume":"90","author":"SP Kuo","year":"2016","journal-title":"Neuron"},{"issue":"51","key":"pgen.1011237.ref088","doi-asserted-by":"crossref","first-page":"13727","DOI":"10.1523\/JNEUROSCI.5741-07.2008","article-title":"Overexpressed transient receptor potential vanilloid 3 ion channels in skin keratinocytes modulate pain sensitivity via prostaglandin E2","volume":"28","author":"SM Huang","year":"2008","journal-title":"J Neurosci"},{"key":"pgen.1011237.ref089","article-title":"Drosophila epidermal cells are intrinsically mechanosensitive and drive nociceptive behavioral outputs","author":"J Yoshino","journal-title":"bioRxiv"},{"issue":"4","key":"pgen.1011237.ref090","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1097\/j.pain.0000000000000092","article-title":"Selective keratinocyte stimulation is sufficient to evoke nociception in mice","volume":"156","author":"Z Pang","year":"2015","journal-title":"Pain"},{"key":"pgen.1011237.ref091","doi-asserted-by":"crossref","first-page":"e33660","DOI":"10.7554\/eLife.33660","article-title":"Structure-based membrane dome mechanism for Piezo mechanosensitivity","volume":"6","author":"YR Guo","year":"2017","journal-title":"Elife"},{"issue":"7693","key":"pgen.1011237.ref092","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature25453","article-title":"Structure of the mechanically activated ion channel Piezo1","volume":"554","author":"K Saotome","year":"2018","journal-title":"Nature"},{"issue":"7773","key":"pgen.1011237.ref093","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/s41586-019-1499-2","article-title":"Force-induced conformational changes in PIEZO1","volume":"573","author":"YC Lin","year":"2019","journal-title":"Nature"},{"issue":"7","key":"pgen.1011237.ref094","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1016\/j.celrep.2016.10.033","article-title":"Piezo1 Channels Are Inherently Mechanosensitive","volume":"17","author":"R Syeda","year":"2016","journal-title":"Cell Rep"},{"issue":"8","key":"pgen.1011237.ref095","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1016\/j.bpj.2021.02.006","article-title":"Molecular dynamics simulations of Piezo1 channel opening by increases in membrane tension","volume":"120","author":"D De Vecchis","year":"2021","journal-title":"Biophys J"},{"key":"pgen.1011237.ref096","article-title":"Direct observation of the conformational states of PIEZO1","author":"EM Mulhall","year":"2023","journal-title":"Nature"},{"key":"pgen.1011237.ref097","doi-asserted-by":"crossref","first-page":"e76574","DOI":"10.7554\/eLife.76574","article-title":"Drosophila mechanical nociceptors preferentially sense localized poking","volume":"11","author":"Z Liu","year":"2022","journal-title":"Elife"},{"issue":"2","key":"pgen.1011237.ref098","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1080\/01677060490894522","article-title":"A modified minimal hemolymph-like solution, HL3.1, for physiological recordings at the neuromuscular junctions of normal and mutant Drosophila larvae","volume":"18","author":"Y Feng","year":"2004","journal-title":"J Neurogenet"},{"issue":"7","key":"pgen.1011237.ref099","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"J Schindelin","year":"2012","journal-title":"Nat Methods"},{"issue":"17","key":"pgen.1011237.ref100","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.1093\/bioinformatics\/btr390","article-title":"Simple Neurite Tracer: open source software for reconstruction, visualization and analysis of neuronal processes","volume":"27","author":"MH Longair","year":"2011","journal-title":"Bioinformatics"},{"issue":"7","key":"pgen.1011237.ref101","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"CA Schneider","year":"2012","journal-title":"Nat Methods"},{"issue":"6","key":"pgen.1011237.ref102","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1016\/0896-6273(94)90437-5","article-title":"Genetic dissection of mechanosensory transduction: mechanoreception-defective mutations of Drosophila","volume":"12","author":"M Kernan","year":"1994","journal-title":"Neuron"},{"key":"pgen.1011237.ref103","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s12859-016-0956-2","article-title":"Trimming of sequence reads alters RNA-Seq gene expression estimates","volume":"17","author":"CR Williams","year":"2016","journal-title":"BMC Bioinformatics"},{"issue":"1","key":"pgen.1011237.ref104","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/nprot.2014.006","article-title":"Full-length RNA-seq from single cells using Smart-seq2","volume":"9","author":"S Picelli","year":"2014","journal-title":"Nat Protoc"},{"issue":"19","key":"pgen.1011237.ref105","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","article-title":"MultiQC: summarize analysis results for multiple tools and samples in a single report","volume":"32","author":"P Ewels","year":"2016","journal-title":"Bioinformatics"},{"issue":"1","key":"pgen.1011237.ref106","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt Removes Adapter Sequences From High-Throughput Sequencing Reads","volume":"17","author":"M. Martin","year":"2011","journal-title":"EMBnet.journal"},{"issue":"5","key":"pgen.1011237.ref107","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nbt.3519","article-title":"Near-optimal probabilistic RNA-seq quantification","volume":"34","author":"NL Bray","year":"2016","journal-title":"Nat Biotechnol"},{"issue":"6","key":"pgen.1011237.ref108","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.devcel.2014.11.029","article-title":"Systematic Study of Drosophila MicroRNA Functions Using a Collection of Targeted Knockout Mutations","volume":"31","author":"YW Chen","year":"2014","journal-title":"Developmental Cell"}],"updated-by":[{"DOI":"10.1371\/journal.pgen.1011237","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T00:00:00Z","timestamp":1715040000000}}],"container-title":["PLOS Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1011237","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T17:43:27Z","timestamp":1715103807000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1011237"}},"subtitle":[],"editor":[{"given":"Fengwei","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,4,25]]},"references-count":108,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1011237","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pgen.1011237","asserted-by":"object"}]},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,25]]}}}