{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T06:54:11Z","timestamp":1775890451973,"version":"3.50.1"},"posted":{"date-parts":[[2025,1,30]]},"group-title":"Neuroscience","reference-count":68,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,1,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Skin-penetrating nematodes are one of the most prevalent causes of disease worldwide \u2013 nearly 15% of the global population is infected with at least one species of skin-penetrating nematode\n                  <jats:sup>1,2<\/jats:sup>\n                  . The World Health Organization has targeted these parasites for elimination by 2030\n                  <jats:sup>3<\/jats:sup>\n                  , but the lack of preventative measures is a major obstacle to this goal. The infective larvae of skin-penetrating nematodes enter hosts through skin\n                  <jats:sup>4<\/jats:sup>\n                  , and blocking skin penetration is an as-yet unexplored approach for preventing infection. However, in order to prevent worm ingress via the skin, an understanding of the behavioral and neural mechanisms that drive skin penetration is required. Here, we describe the skin-penetration behaviors of the human-infective threadworm\n                  <jats:italic>Strongyloides stercoralis<\/jats:italic>\n                  . Using fluorescently labeled worms to enable visualization on the skin coupled with time-lapse microscopy, we show that\n                  <jats:italic>S. stercoralis<\/jats:italic>\n                  engages in repeated cycles of pushing, puncturing, and crawling on the skin surface before penetrating the skin. Pharmacological inhibition of dopamine signaling inhibits these behaviors in\n                  <jats:italic>S. stercoralis<\/jats:italic>\n                  and the human hookworm\n                  <jats:italic>Ancylostoma ceylanicum,<\/jats:italic>\n                  suggesting a critical role for dopamine signaling in driving skin penetration across distantly related nematodes. CRISPR-mediated disruption of dopamine biosynthesis and chemogenetic silencing of dopaminergic neurons also inhibit skin penetration. Finally, inactivation of the TRPN channel TRP-4, which is expressed in the dopaminergic neurons, blocks skin penetration on both rat and human skin. Our results suggest that drugs targeting TRP-4 and other nematode-specific components of the dopaminergic pathway could be developed into topical prophylactics that block skin penetration, thereby preventing infections.\n                <\/jats:p>","DOI":"10.1101\/2025.01.29.635547","type":"posted-content","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T10:40:13Z","timestamp":1738233613000},"source":"Crossref","is-referenced-by-count":0,"title":["Dopamine signaling drives skin invasion by human-infective nematodes"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8612-0016","authenticated-orcid":false,"given":"Ruhi","family":"Patel","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7845-1296","authenticated-orcid":false,"given":"Aracely Garcia","family":"Romero","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0887-2044","authenticated-orcid":false,"given":"Astra S.","family":"Bryant","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Biophysics, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3356-9864","authenticated-orcid":false,"given":"George W.","family":"Agak","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0260-3174","authenticated-orcid":false,"given":"Elissa A.","family":"Hallem","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA"},{"name":"Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041023195992000_2025.01.29.635547v1.1","doi-asserted-by":"publisher","DOI":"10.1177\/2058739220959915"},{"key":"2026041023195992000_2025.01.29.635547v1.2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens9060468"},{"key":"2026041023195992000_2025.01.29.635547v1.3","unstructured":"WHO. 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