{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:08:10Z","timestamp":1781104090511,"version":"3.54.1"},"reference-count":73,"publisher":"National Academy of Sciences","issue":"43","license":[{"start":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T00:00:00Z","timestamp":1697673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS076542"],"award-info":[{"award-number":["NS076542"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Bristol Myers Squibb","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,10,24]]},"abstract":"<jats:p>\n                    Thalidomide has a dark history as a teratogen, but in recent years, its derivates have been shown to function as potent chemotherapeutic agents. These drugs bind cereblon (CRBN), the substrate receptor of an E3 ubiquitin ligase complex, and modify its degradation targets. Despite these insights, remarkably little is known about the normal function of cereblon in development. Here, we employ\n                    <jats:italic>Ciona<\/jats:italic>\n                    , a simple invertebrate chordate, to identify endogenous Crbn targets. In\n                    <jats:italic>Ciona, Crbn<\/jats:italic>\n                    is specifically expressed in developing muscles during tail elongation before they acquire contractile activity.\n                    <jats:italic>Crbn<\/jats:italic>\n                    expression is activated by Mrf, the ortholog of MYOD1, a transcription factor important for muscle differentiation. CRISPR\/Cas9-mediated mutations of\n                    <jats:italic>Crbn<\/jats:italic>\n                    lead to precocious onset of muscle contractions. By contrast, overexpression of\n                    <jats:italic>Crbn<\/jats:italic>\n                    delays contractions and is associated with decreased expression of contractile protein genes such as troponin. This reduction is possibly due to reduced Mrf protein levels without altering\n                    <jats:italic>Mrf<\/jats:italic>\n                    mRNA levels. Our findings suggest that Mrf and Crbn form a negative feedback loop to control the precision of muscle differentiation during tail elongation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2309989120","type":"journal-article","created":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T13:43:25Z","timestamp":1697723005000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":7,"title":["Cereblon influences the timing of muscle differentiation in\n                    <i>Ciona<\/i>\n                    tadpoles"],"prefix":"10.1073","volume":"120","author":[{"given":"Juanjuan","family":"Long","sequence":"first","affiliation":[{"name":"Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Mariossi","sequence":"additional","affiliation":[{"name":"Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Cao","sequence":"additional","affiliation":[{"name":"Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongying","family":"Mo","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel W.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Levine","sequence":"additional","affiliation":[{"name":"Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544"},{"name":"Department of Molecular Biology, Princeton University, Princeton, NJ 08544"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8439-8228","authenticated-orcid":false,"given":"Laurence A.","family":"Lemaire","sequence":"additional","affiliation":[{"name":"Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544"},{"name":"Department of Biology, Saint Louis University, St. Louis, MO 63103"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,10,19]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420380303"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/00039896.1962.10663250"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(61)90927-8"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1177319"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","unstructured":"K. A. Donovan Thalidomide promotes degradation of SALL4 a transcription factor implicated in Duane Radial Ray syndrome. Elife 7 e38430 (2018). e38430","DOI":"10.7554\/eLife.38430"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-018-0129-x"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020105375"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.120.303069"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/76014"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1421949112"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-03-0996"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.9.2943"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1244851"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12708"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1244917"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.2337\/db12-1030"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2011.09.039"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000146196.01316.A2"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2019.04.007"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25634-z"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/jez.1400020202"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1123404"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(85)90102-2"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/35055568"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.066910"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.9.1711"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2006.09.043"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.173104"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2021.12.012"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2002.0582"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000714"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1385-y"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","unstructured":"R. J. White A high-resolution mRNA expression time course of embryonic development in zebrafish. Elife 6 e30860 (2017). e30860","DOI":"10.7554\/eLife.30860"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.10.5670"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.20.5964"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2091-6-27"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M611513200"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608748200"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.21.2602"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80660-1"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90514-D"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.861201"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.15.3323"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005603"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.2035311"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2007.07.013"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001192"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005467"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111832"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.prot5344"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.prot5345"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature15758"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.078485"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abf7452"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-9624-7_23"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.052024999"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.114488"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1158170"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.5.5.627"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2413"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw398"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2017.03.003"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.350164.122"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph17041340"},{"key":"e_1_3_4_66_2","unstructured":"R Core Team R: A Language and Environment for Statistical Computing (R version is v4.2.1 R Core Team Vienna 2015). https:\/\/www.R-project.org\/."},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.2108\/zsj.22.837"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw313"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt276"},{"key":"e_1_3_4_72_2","doi-asserted-by":"crossref","unstructured":"J. Long M. S. Levine L. A. Lemaire Cereblon influences the timing of muscle differentiation in Ciona tadpoles. Gene Expression Omnibus (GEO). https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE241857. Deposited 29 August 2023.","DOI":"10.1101\/2022.08.16.504204"},{"key":"e_1_3_4_73_2","unstructured":"A. Mariossi M. S. Levine L. A. Lemaire Cereblon influences the timing of muscle differentiation in Ciona tadpoles. GitHub. https:\/\/github.com\/LemaireLabAtSLU\/Ciona-Cereblon. Deposited 29 August 2023."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2309989120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T13:43:50Z","timestamp":1697723030000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2309989120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,19]]},"references-count":73,"journal-issue":{"issue":"43","published-print":{"date-parts":[[2023,10,24]]}},"alternative-id":["10.1073\/pnas.2309989120"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2309989120","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,19]]},"assertion":[{"value":"2023-06-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2309989120"}}