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The first molecularly recognizable step of thyroid development is the specification of thyroid precursors in anterior foregut endoderm. Recent studies have identified crucial roles of FGF and BMP signaling in thyroid specification, but the interplay between signaling cues and thyroid transcription factors remained elusive. By analyzing Pax2a and Nkx2.4b expression dynamics in relation to endodermal FGF and BMP signaling activities in zebrafish embryos, we identified a Pax2a-expressing thyroid progenitor population that shows enhanced FGF signaling but lacks Nkx2.4b expression and BMP signaling. Concurrent with upregulated BMP signaling, a subpopulation of these progenitors subsequently differentiates into lineage-committed thyroid precursors co-expressing Pax2a and Nkx2.4b. Timed manipulation of FGF\/BMP activities suggests a model in which FGF signaling primarily regulates Pax2a expression, whereas BMP signaling regulates both Pax2a and Nkx2.4b expression. Our observation of similar expression dynamics of Pax8 and Nkx2-1 in mouse embryos suggests that this refined model of thyroid cell specification is evolutionarily conserved in mammals.<\/jats:p>","DOI":"10.1242\/dev.201023","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T09:45:29Z","timestamp":1683884729000},"source":"Crossref","is-referenced-by-count":9,"title":["Mesodermal FGF and BMP govern the sequential stages of zebrafish thyroid specification"],"prefix":"10.1242","volume":"150","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2664-2098","authenticated-orcid":false,"given":"Benoit","family":"Haerlingen","sequence":"first","affiliation":[{"name":"Institute of Interdisciplinary Research in Molecular Human Biology (IRIBHM), Universit\u00e9 Libre de Bruxelles 1 , 1070 Brussels , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Opitz","sequence":"additional","affiliation":[{"name":"Institute of Interdisciplinary Research in Molecular Human Biology (IRIBHM), Universit\u00e9 Libre de Bruxelles 1 , 1070 Brussels , Belgium"},{"name":"Institute of Experimental Pediatric Endocrinology, Charit\u00e9 Universit\u00e4tsmedizin 2 , 13353 Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Vandernoot","sequence":"additional","affiliation":[{"name":"Centre of Human Genetics, Erasmus Hospital, Universit\u00e9 Libre de Bruxelles 3 , 1070 Brussels , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8539-4429","authenticated-orcid":false,"given":"Angelo","family":"Molinaro","sequence":"additional","affiliation":[{"name":"University of Pisa, 56126 Pisa 4 Department of Experimental and Clinical Medicine, Endocrinology Unit , , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghna Parakkal","family":"Shankar","sequence":"additional","affiliation":[{"name":"Institute of Interdisciplinary Research in Molecular Human Biology (IRIBHM), Universit\u00e9 Libre de Bruxelles 1 , 1070 Brussels , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Gillotay","sequence":"additional","affiliation":[{"name":"Institute of Interdisciplinary Research in Molecular Human Biology (IRIBHM), Universit\u00e9 Libre de Bruxelles 1 , 1070 Brussels , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Trubiroha","sequence":"additional","affiliation":[{"name":"Institute of Interdisciplinary Research in Molecular Human Biology (IRIBHM), Universit\u00e9 Libre de Bruxelles 1 , 1070 Brussels , Belgium"},{"name":"German Federal Institute for Risk Assessment (BfR) 5 Department Chemicals and Product Safety , , 10589 Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6869-9941","authenticated-orcid":false,"given":"Sabine","family":"Costagliola","sequence":"additional","affiliation":[{"name":"Institute of Interdisciplinary Research in Molecular Human Biology (IRIBHM), Universit\u00e9 Libre de Bruxelles 1 , 1070 Brussels , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2023,5,16]]},"reference":[{"key":"2023051608245033400_DEV201023C1","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1002\/dvdy.20831","article-title":"Analysis of origin and growth of the thyroid gland in zebrafish","volume":"235","author":"Alt","year":"2006","journal-title":"Dev. 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