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We previously demonstrated using gene knockout (KO) experiments on the ascidian\n                    <jats:italic>Ciona robusta<\/jats:italic>\n                    that the thyroid\u2010related transcription factors, Nkx2\u20101 and FoxE, were associated with endostyle development, and also that Nkx2\u20101 regulated the expression of\n                    <jats:italic>TPO<\/jats:italic>\n                    via FoxE, even though the expression of\n                    <jats:italic>Pax2\/5\/8<\/jats:italic>\n                    homologs was not affected. In the present study, which involved detailed observations of\n                    <jats:italic>Ciona Nkx2\u20101<\/jats:italic>\n                    \u2010KO and\n                    <jats:italic>FoxE<\/jats:italic>\n                    \u2010KO specimens, we found that ectopic bulged structures neighboring the hypoplastic endostyle occasionally emerged. In\u00a0situ hybridization revealed that the ectopic bulged structures expressed\n                    <jats:italic>TPO<\/jats:italic>\n                    and\n                    <jats:italic>Pax2\/5\/8<\/jats:italic>\n                    homologs. Further KO experiments on\n                    <jats:italic>Ciona Pax2\/5\/8<\/jats:italic>\n                    homologs revealed no effects on endostyle development or\n                    <jats:italic>TPO<\/jats:italic>\n                    expression. These results suggest that, in addition to the established \u201cNkx2\u20101 \u2013&gt;\n                    <jats:italic>FoxE<\/jats:italic>\n                    \u2010FoxE \u2013&gt;\n                    <jats:italic>TPO<\/jats:italic>\n                    \u201d pathway, the ventral pharynx offers an insight into a potential relationship between Pax2\/5\/8 homologs and\n                    <jats:italic>TPO<\/jats:italic>\n                    . Accordingly, ascidians may show that the ventral pharyngeal endoderm possessed multiple gene regulatory networks for\n                    <jats:italic>TPO<\/jats:italic>\n                    expression prior to the evolutionary divergence leading to the vertebrate follicular thyroid.\n                  <\/jats:p>","DOI":"10.1002\/dvg.70064","type":"journal-article","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T05:40:20Z","timestamp":1783143620000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ectopic Bulged Structures in\n                    <i>Nkx2\u20101<\/i>\n                    \u2010\n                    <scp>KO<\/scp>\n                    and\n                    <scp>\n                      <i>FoxE<\/i>\n                    <\/scp>\n                    \u2010\n                    <scp>KO<\/scp>\n                    Juveniles of\n                    <scp>\n                      <i>C<\/i>\n                    <\/scp>\n                    <i>iona robusta<\/i>\n                    : Insights Into the Parallel Gene Regulatory System Before the Evolution of Thyroid Follicular Cells"],"prefix":"10.1002","volume":"64","author":[{"given":"Hiroki","family":"Kawamorita","sequence":"first","affiliation":[{"name":"Department of Biology, Graduate School of Science Chiba University  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizuki","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Biology, Graduate School of Science Chiba University  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7161-8367","authenticated-orcid":false,"given":"Yasunori","family":"Sasakura","sequence":"additional","affiliation":[{"name":"Shimoda Marine Research Center University of Tsukuba  Shizuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michio","family":"Ogasawara","sequence":"additional","affiliation":[{"name":"Department of Biology, Graduate School of Science Chiba University  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"e_1_2_1_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr218"},{"key":"e_1_2_1_10_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2012\u20101015"},{"key":"e_1_2_1_10_4_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.3.589"},{"key":"e_1_2_1_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks608"},{"key":"e_1_2_1_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jez.1401880111"},{"key":"e_1_2_1_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00560154"},{"key":"e_1_2_1_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441\u2010006\u20100220\u20106"},{"key":"e_1_2_1_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20401"},{"key":"e_1_2_1_10_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adi9035"},{"key":"e_1_2_1_10_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology12020245"},{"key":"e_1_2_1_10_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.654569"},{"key":"e_1_2_1_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441\u2010017\u20102627\u20107"},{"key":"e_1_2_1_10_14_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.145615"},{"key":"e_1_2_1_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004270050309"},{"key":"e_1_2_1_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1097\u2010010x(19990815)285:2<158::aid\u2010jez8>3.0.co;2\u20100"},{"key":"e_1_2_1_10_17_1","doi-asserted-by":"publisher","DOI":"10.2108\/zsj.16.559"},{"key":"e_1_2_1_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00427\u2010003\u20100342\u20108"},{"key":"e_1_2_1_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463\u20106395.1963.tb00411.x"},{"key":"e_1_2_1_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2021.05.021"},{"key":"e_1_2_1_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/gtc.12050"},{"key":"e_1_2_1_10_22_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.22.5149"},{"key":"e_1_2_1_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep03379"},{"key":"e_1_2_1_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20107128\u20102_19"},{"key":"e_1_2_1_10_25_1","volume-title":"Chordate Origins and Evolution. 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