{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:47:00Z","timestamp":1790484420842,"version":"4.1.0"},"reference-count":60,"publisher":"The Company of Biologists","issue":"19","license":[{"start":{"date-parts":[[2021,10,4]],"date-time":"2021-10-04T00:00:00Z","timestamp":1633305600000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"The Netherlands CardioVascular Research Initiative"},{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012524","name":"Nederlandse Federatie van Universitair Medische Centra","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012524","id-type":"DOI","asserted-by":"crossref"}]},{"name":"ZonMw"},{"name":"Koninklijke Nederlandse Akademie van Wetenschappen","award":["2017T059"],"award-info":[{"award-number":["2017T059"]}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"crossref","award":["CH\/11\/1\/28798"],"award-info":[{"award-number":["CH\/11\/1\/28798"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Fibroblasts are activated to repair the heart following injury. Fibroblast activation in the mammalian heart leads to a permanent fibrotic scar that impairs cardiac function. In other organisms, such as zebrafish, cardiac injury is followed by transient fibrosis and scar-free regeneration. The mechanisms that drive scarring versus scar-free regeneration are not well understood. Here, we show that the homeobox-containing transcription factor Prrx1b is required for scar-free regeneration of the zebrafish heart as the loss of Prrx1b results in excessive fibrosis and impaired cardiomyocyte proliferation. Through lineage tracing and single-cell RNA sequencing, we find that Prrx1b is activated in epicardial-derived cells where it restricts TGF\u03b2 ligand expression and collagen production. Furthermore, through combined in vitro experiments in human fetal epicardial-derived cells and in vivo rescue experiments in zebrafish, we conclude that Prrx1 stimulates Nrg1 expression and promotes cardiomyocyte proliferation. Collectively, these results indicate that Prrx1 is a key transcription factor that balances fibrosis and regeneration in the injured zebrafish heart.<\/jats:p>\n                  <jats:p>This article has an associated \u2018The people behind the papers\u2019 interview.<\/jats:p>","DOI":"10.1242\/dev.198937","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T14:07:55Z","timestamp":1630937275000},"source":"Crossref","is-referenced-by-count":41,"title":["Prrx1b restricts fibrosis and promotes Nrg1-dependent cardiomyocyte proliferation during zebrafish heart regeneration"],"prefix":"10.1242","volume":"148","author":[{"given":"Dennis E. M.","family":"de Bakker","sequence":"first","affiliation":[{"name":"Hubrecht Institute-KNAW and University Medical Center Utrecht, 3584CT Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Bouwman","sequence":"additional","affiliation":[{"name":"Hubrecht Institute-KNAW and University Medical Center Utrecht, 3584CT Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Dronkers","sequence":"additional","affiliation":[{"name":"Department of Cell and Chemical Biology, Leiden University Medical Centre, 2333ZC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filipa C.","family":"Sim\u00f5es","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R.","family":"Riley","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9344-6746","authenticated-orcid":false,"given":"Marie-Jos\u00e9","family":"Goumans","sequence":"additional","affiliation":[{"name":"Department of Cell and Chemical Biology, Leiden University Medical Centre, 2333ZC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke M.","family":"Smits","sequence":"additional","affiliation":[{"name":"Department of Cell and Chemical Biology, Leiden University Medical Centre, 2333ZC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9418-0422","authenticated-orcid":false,"given":"Jeroen","family":"Bakkers","sequence":"additional","affiliation":[{"name":"Hubrecht Institute-KNAW and University Medical Center Utrecht, 3584CT Utrecht, The Netherlands"},{"name":"Department of Pediatric Cardiology, University Medical Centre Utrecht, 3584CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2021,10,4]]},"reference":[{"key":"2021101115491835900_DEV198937C1","doi-asserted-by":"publisher","first-page":"2139","DOI":"10.1242\/dev.079970","article-title":"The bHLH transcription factor Tcf21 is required for lineage-specific EMT of cardiac fibroblast progenitors","volume":"139","author":"Acharya","year":"2012","journal-title":"Development"},{"key":"2021101115491835900_DEV198937C2","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1177\/0023677219869037","article-title":"Zebrafish: Housing and husbandry recommendations","volume":"54","author":"Alestr\u00f6m","year":"2019","journal-title":"Lab. 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