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Previous studies have revealed much about the neural circuits and sensory molecules in mechanical nociception, but the cellular mechanisms adopted by nociceptors in force detection remain elusive. To address this issue, we study the mechanosensation of a fly larval nociceptor (class IV da neurons, c4da) using a customized mechanical device. We find that c4da are sensitive to mN-scale forces and make uniform responses to the forces applied at different dendritic regions. Moreover, c4da showed a greater sensitivity to localized forces, consistent with them being able to detect the poking of sharp objects, such as wasp ovipositor. Further analysis reveals that high morphological complexity, mechanosensitivity to lateral tension and possibly also active signal propagation in dendrites contribute to the sensory features of c4da. In particular, we discover that Piezo and Ppk1\/Ppk26, two key mechanosensory molecules, make differential but additive contributions to the mechanosensitivity of c4da. In all, our results provide updates into understanding how c4da process mechanical signals at the cellular level and reveal the contributions of key molecules.<\/jats:p>","DOI":"10.7554\/elife.76574","type":"journal-article","created":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T07:31:24Z","timestamp":1665041484000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.76574","source":"Crossref","is-referenced-by-count":20,"title":["Drosophila mechanical nociceptors preferentially sense localized poking"],"prefix":"10.7554","volume":"11","author":[{"given":"Zhen","family":"Liu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03cve4549","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Life Sciences, Tsinghua University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Hua","family":"Wu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03cve4549","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Life Sciences, Tsinghua University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi-Xuan","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03cve4549","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Life Sciences, Tsinghua University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Zhen","family":"Lin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03cve4549","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi-Qiao","family":"Feng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03cve4549","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03cve4549","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7915-8094","authenticated-orcid":true,"given":"Xin","family":"Liang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03cve4549","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Life Sciences, Tsinghua University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2022,10,6]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"3222","DOI":"10.1016\/j.bpj.2021.06.001","article-title":"Focal laser stimulation of fly nociceptors activates distinct axonal and dendritic Ca2+ signals","volume":"120","author":"Basak","year":"2021","journal-title":"Biophysical Journal"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.26016","article-title":"Nociceptive interneurons control modular motor pathways to promote escape behavior in Drosophila","volume":"7","author":"Burgos","year":"2018","journal-title":"eLife"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"E7822","DOI":"10.1073\/pnas.1706162114","article-title":"Mechanisms of ovipositor insertion and steering of a parasitic wasp","volume":"114","author":"Cerkvenik","year":"2017","journal-title":"PNAS"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nrm2595","article-title":"Neurosensory mechanotransduction","volume":"10","author":"Chalfie","year":"2009","journal-title":"Nature Reviews. 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