{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T14:31:20Z","timestamp":1771338680699,"version":"3.50.1"},"reference-count":76,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,25]],"date-time":"2019-12-25T00:00:00Z","timestamp":1577232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007364","name":"Fondazione CRT","doi-asserted-by":"publisher","award":["RF 2014.0814"],"award-info":[{"award-number":["RF 2014.0814"]}],"id":[{"id":"10.13039\/100007364","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["2010W87LBJ_005"],"award-info":[{"award-number":["2010W87LBJ_005"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The G protein-coupled cannabinoid receptors type 1 (CB1R) and type 2 (CB2R), and their endocannabinoid (eCBs) ligands, have been implicated in several aspects of brain wiring during development. Here we aim to assess whether interfering with CB1R affects development, neuritogenesis and pathfinding of GnRH and AgRP neurons, forebrain neurons that control respectively reproduction and appetite. We pharmacologically and genetically interfered with CB1R in zebrafish strains with fluorescently labeled GnRH3 and the AgRP1 neurons. By applying CB1R antagonists we observed a reduced number of GnRH3 neurons, fiber misrouting and altered fasciculation. Similar phenotypes were observed by CB1R knockdown. Interfering with CB1R also resulted in a reduced number, misrouting and poor fasciculation of the AgRP1 neuron\u2019s axonal projections. Using a bioinformatic approach followed by qPCR validation, we have attempted to link CB1R functions with known guidance and fasciculation proteins. The search identified stathmin-2, a protein controlling microtubule dynamics, previously demonstrated to be coexpressed with CB1R and now shown to be downregulated upon interference with CB1R in zebrafish. Together, these results raise the likely possibility that embryonic exposure to low doses of CB1R-interfering compounds could impact on the development of the neuroendocrine systems controlling sexual maturation, reproduction and food intake.<\/jats:p>","DOI":"10.3390\/ijms21010168","type":"journal-article","created":{"date-parts":[[2019,12,25]],"date-time":"2019-12-25T11:07:48Z","timestamp":1577272068000},"page":"168","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Interference with the Cannabinoid Receptor CB1R Results in Miswiring of GnRH3 and AgRP1 Axons in Zebrafish Embryos"],"prefix":"10.3390","volume":"21","author":[{"given":"Giulia","family":"Zuccarini","sequence":"first","affiliation":[{"name":"Department of Life Sciences and Systems Biology, University of Torino, 10123 Torino, Italy"},{"name":"Department of Molecular Biotechnologies and Health Sciences, University of Torino, 10126 Torino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6432-4931","authenticated-orcid":false,"given":"Ilaria","family":"D\u2019Atri","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Systems Biology, University of Torino, 10123 Torino, Italy"},{"name":"Department of Molecular Biotechnologies and Health Sciences, University of Torino, 10126 Torino, Italy"},{"name":"Wellcome Wolfson Centre for Medical Research, University of Exeter, Exeter EX2 5DW, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika","family":"Cottone","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Systems Biology, University of Torino, 10123 Torino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8501-6199","authenticated-orcid":false,"given":"Ken","family":"Mackie","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences, Gill Center for Biomolecular Science, Indiana University, Bloomington, IN 47405, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inbal","family":"Shainer","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, The George S. Wise Faculty of Life Sciences and Sagol School of Neuroscience, Tel-Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoav","family":"Gothilf","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, The George S. Wise Faculty of Life Sciences and Sagol School of Neuroscience, Tel-Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Provero","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnologies and Health Sciences, University of Torino, 10126 Torino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrizia","family":"Bovolin","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Systems Biology, University of Torino, 10123 Torino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgio Roberto","family":"Merlo","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnologies and Health Sciences, University of Torino, 10126 Torino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"327","DOI":"10.2165\/00003088-200342040-00003","article-title":"Pharmacokinetics and Pharmacodynamics of Cannabinoids","volume":"42","author":"Grotenhermen","year":"2003","journal-title":"Clin. 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