{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T14:10:51Z","timestamp":1773065451325,"version":"3.50.1"},"reference-count":65,"publisher":"Wiley","issue":"7-8","license":[{"start":{"date-parts":[[2019,4,30]],"date-time":"2019-04-30T00:00:00Z","timestamp":1556582400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["2015\u201003780"],"award-info":[{"award-number":["2015\u201003780"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genesis"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Retinoic acid (RA), the active metabolite of vitamin A, functions through nuclear receptors, one of which is the retinoic acid receptor (RAR). Though the RAR is essential for various aspects of vertebrate development, little is known about the role of RAR in nonchordate invertebrates. Here, we examined the potential role of an invertebrate RAR in mediating chemotropic effects of retinoic acid. The RAR of the protostome <jats:styled-content style=\"fixed-case\"><jats:italic>Lymnaea stagnalis<\/jats:italic><\/jats:styled-content> is present in the growth cones of regenerating cultured motorneurons, and a synthetic RAR agonist (EC23), was able to mimic the effects of retinoic acid in inducing growth cone turning. We also examined the ability of the natural retinoids, all\u2010<jats:italic>trans<\/jats:italic> RA and 9\u2010<jats:italic>cis<\/jats:italic> RA, as well as the synthetic RAR agonists, to disrupt embryonic development in <jats:italic>Lymnaea<\/jats:italic>. Developmental defects included delays in embryo hatching, arrested eye, and shell development, as well as more severe abnormalities such as halted development. Developmental defects induced by some (but not all) synthetic RAR agonists were found to mimic those induced by addition of high concentrations of the natural retinoid isomers. These pharmacological data support a possible physiological role for the RAR in axon guidance and embryonic development of an invertebrate protostome species.<\/jats:p>","DOI":"10.1002\/dvg.23301","type":"journal-article","created":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T03:22:40Z","timestamp":1556680960000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pharmacological evidence for the role of RAR in axon guidance and embryonic development of a protostome species"],"prefix":"10.1002","volume":"57","author":[{"given":"Alysha","family":"Johnson","sequence":"first","affiliation":[{"name":"Department of Biological Sciences Brock University  St. Catharines Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"de Hoog","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Brock University  St. Catharines Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Tolentino","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Brock University  St. Catharines Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara","family":"Nasser","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Brock University  St. Catharines Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8927-6844","authenticated-orcid":false,"given":"Gaynor E.","family":"Spencer","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Brock University  St. Catharines Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,4,30]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2009.08.029"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2008.09.017"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.1.30"},{"issue":"24","key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"16689","DOI":"10.1016\/S0021-9258(19)89445-0","article-title":"Binding of 9\u2010cis\u2010retinoic acid and all\u2010trans\u2010retinoic acid to retinoic acid receptors alpha, beta, and gamma. Retinoic acid receptor gamma binds all\u2010trans\u2010retinoic acid preferentially over 9\u2010cis\u2010retinoic acid","volume":"269","author":"Allenby G.","year":"1994","journal-title":"Journal of Biological Chemistry"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.08.012"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(92)90842-9"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.22294"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1677\/jme.1.01766"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22769"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2010.03.023"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jez.b.22604"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2008.11.040"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1039\/b808574a"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2010.08.022"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1039\/c3mb25505k"},{"issue":"14","key":"e_1_2_6_17_1","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1242\/jcs.113.14.2567","article-title":"The role of retinoic acid receptors in neurite outgrowth from different populations of embryonic mouse dorsal root ganglia","volume":"113","author":"Corcoran J.","year":"2000","journal-title":"Journal of Cell Science"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00046"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-169X.1993.00357.x"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3932"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-2797(00)00261-1"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3192-08.2008"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2006.02.018"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2005.02.019"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.11.2592"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2921-09.2009"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(99)00202-6"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.61.2.334"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1844"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1181"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aao1261"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(90)91007-F"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90479-V"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jez.1402720607"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/07924259.1994.9672405"},{"key":"e_1_2_6_36_1","first-page":"3523","article-title":"New benzoic acid derivatives with retinoid activity: Lack of direct correlation between biological activity and binding to cellular retinoic acid binding protein","volume":"47","author":"Jetten A. M.","year":"1987","journal-title":"Cancer Research"},{"issue":"2","key":"e_1_2_6_37_1","first-page":"397","article-title":"RAR\u03b1 is a regulatory factor for am\u201080\u2010induced cell growth inhibition of hematologic malignant cells","volume":"31","author":"Jimi S.","year":"2007","journal-title":"International Journal of Oncology"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601808"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.12-04-01253.1992"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn963"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2212"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0736-5748(98)00046-X"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804801105"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1039\/b817912c"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1567-133X(03)00051-6"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007112130414"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712132105"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0807740105"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjz-2016-0279"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2018.02.010"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13281"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.04534.x"},{"issue":"3","key":"e_1_2_6_53_1","first-page":"589","article-title":"Gross congenital malformations. Animal model: Treatment of various species with a large dose of vitamin A at known stages in pregnancy","volume":"66","author":"Shenefelt R. E.","year":"1972","journal-title":"American Journal of Pathology"},{"key":"e_1_2_6_54_1","first-page":"393","article-title":"Am80 induces neuronal differentiation in a human neuroblastoma NH\u201012 cell line","volume":"26","author":"Shiohira H.","year":"2010","journal-title":"International Journal of Molecular Medicine"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/jez.b.21139"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/0300-9629(89)90024-8"},{"key":"e_1_2_6_57_1","first-page":"1938","article-title":"Structural and functional insights into the ligand binding domain of a non\u2010duplicated RXR from the invertebrate chordate amphioxus","volume":"284","author":"Tocchini\u2010Valentini G.","year":"2009","journal-title":"Journal of Biochemistry"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquatox.2013.09.008"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.2307\/1543098"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00458.2014"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0176024"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.23.13459"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.00541"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.2003.00230.x"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.01-09-01008.1981"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/128.2.455S"}],"container-title":["genesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fdvg.23301","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dvg.23301","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/dvg.23301","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dvg.23301","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T06:23:53Z","timestamp":1694327033000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/dvg.23301"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,30]]},"references-count":65,"journal-issue":{"issue":"7-8","published-print":{"date-parts":[[2019,7]]}},"alternative-id":["10.1002\/dvg.23301"],"URL":"https:\/\/doi.org\/10.1002\/dvg.23301","archive":["Portico"],"relation":{},"ISSN":["1526-954X","1526-968X"],"issn-type":[{"value":"1526-954X","type":"print"},{"value":"1526-968X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,30]]},"assertion":[{"value":"2018-12-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e23301"}}