{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T15:29:47Z","timestamp":1760369387811,"version":"3.37.3"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,10,10]],"date-time":"2017-10-10T00:00:00Z","timestamp":1507593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000882","name":"University of Aberdeen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000882","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Anatomy"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Thalidomide notoriously caused severe birth defects, particularly to the limbs, in those exposed <jats:italic>in utero<\/jats:italic> following maternal use of the drug to treat morning sickness. How the drug caused these birth defects remains unclear. Many theories have been proposed including actions on the forming blood vessels. However, thalidomide survivors also have altered nerve patterns and the drug is known for its neurotoxic actions in adults following prolonged use. We have previously shown that <jats:styled-content style=\"fixed-case\">CPS<\/jats:styled-content>49, an anti\u2010angiogenic analog of thalidomide, causes a range of limb malformations in a time\u2010sensitive manner in chicken embryos. Here we investigated whether <jats:styled-content style=\"fixed-case\">CPS<\/jats:styled-content>49 also is neurotoxic and whether effects on nerve development impact upon limb development. We found that <jats:styled-content style=\"fixed-case\">CPS<\/jats:styled-content>49 is neurotoxic, just like thalidomide, and can cause some neuronal loss late developing chicken limbs, but only when the limb is already innervated. However, <jats:styled-content style=\"fixed-case\">CPS<\/jats:styled-content>49 exposure does not cause defects in limb size when added to late developing chicken limbs. In contrast, in early limb buds which are not innervated, <jats:styled-content style=\"fixed-case\">CPS<\/jats:styled-content>49 exposure affects limb area significantly. To investigate in more detail the role of neurotoxicity and its impact on chicken limb development we inhibited nerve innervation at a range of developmental timepoints through using \u03b2\u2010bungarotoxin. We found that neuronal inhibition or ablation before, during or after limb outgrowth and innervation does not result in obvious limb cartilage patterning or number changes. We conclude that while <jats:styled-content style=\"fixed-case\">CPS<\/jats:styled-content>49 is neurotoxic, given the late innervation of the developing limb, and that neuronal inhibition\/ablation throughout limb development does not cause similar limb patterning anomalies to those seen in thalidomide survivors, nerve defects are not the primary underlying cause of the severe limb patterning defects induced by <jats:styled-content style=\"fixed-case\">CPS<\/jats:styled-content>49\/thalidomide.<\/jats:p>","DOI":"10.1111\/joa.12712","type":"journal-article","created":{"date-parts":[[2017,10,11]],"date-time":"2017-10-11T03:32:43Z","timestamp":1507692763000},"page":"568-574","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<scp>CPS<\/scp>49\u2010induced neurotoxicity does not cause limb patterning anomalies in developing chicken embryos"],"prefix":"10.1111","volume":"232","author":[{"given":"Chris","family":"Mahony","sequence":"first","affiliation":[{"name":"School of Medicine, Medical Sciences and Nutrition Institute of Medical Sciences University of Aberdeen Aberdeen UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott","family":"McMenemy","sequence":"additional","affiliation":[{"name":"School of Medicine, Medical Sciences and Nutrition Institute of Medical Sciences University of Aberdeen Aberdeen UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra J.","family":"Rafipay","sequence":"additional","affiliation":[{"name":"School of Medicine, Medical Sciences and Nutrition Institute of Medical Sciences University of Aberdeen Aberdeen UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaunna\u2010Leigh","family":"Beedie","sequence":"additional","affiliation":[{"name":"School of Medicine, Medical Sciences and Nutrition Institute of Medical Sciences University of Aberdeen Aberdeen UK"},{"name":"Molecular Pharmacology Section Genitourinary Malignancies Branch Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas Rosa","family":"Fraga","sequence":"additional","affiliation":[{"name":"School of Medicine, Medical Sciences and Nutrition Institute of Medical Sciences University of Aberdeen Aberdeen UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"G\u00fctschow","sequence":"additional","affiliation":[{"name":"Pharmaceutical Institute University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William D.","family":"Figg","sequence":"additional","affiliation":[{"name":"Molecular Pharmacology Section Genitourinary Malignancies Branch Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD 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