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Here, we report that transcription factors (TFs) Brn-3a (POU4F1) and Brn-3b (POU4F2) are important for normal cardiac development. Brn-3a directly represses Brn-3b promoter in cardiomyocytes and consequently Brn-3a knockout (KO) mutant hearts express increased Brn-3b mRNA during mid-gestation, which is linked to hyperplastic growth associated with elevated cyclin D1, a known Brn-3b target gene. However, during late gestation, Brn-3b can cooperate with p53 to enhance transcription of pro-apoptotic genes e.g. Bax, thereby increasing apoptosis and contribute to morphological defects such as non-compaction, ventricular wall\/septal thinning and increased crypts\/fissures, which may cause lethality of Brn-3a KO mutants soon after birth. Despite this, early embryonic lethality in e9.5 double KO (Brn-3a<jats:sup>\u2212\/\u2212<\/jats:sup>\u2009:\u2009Brn-3b<jats:sup>\u2212\/\u2212<\/jats:sup>) mutants indicate essential functions with partial redundancy during early embryogenesis. High conservation between mammals and zebrafish (ZF) Brn-3b (87%) or Brn-3a (76%) facilitated use of ZF embryos to study potential roles in developing heart. Double morphant embryos targeted with morpholino oligonucleotides to both TFs develop significant cardiac defects (looping abnormalities and valve defects) suggesting essential roles for Brn-3a and Brn-3b in developing hearts.<\/jats:p>","DOI":"10.1038\/cddis.2017.185","type":"journal-article","created":{"date-parts":[[2017,6,8]],"date-time":"2017-06-08T12:42:52Z","timestamp":1496925772000},"page":"e2861-e2861","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Essential but partially redundant roles for POU4F1\/Brn-3a and POU4F2\/Brn-3b transcription factors in the developing heart"],"prefix":"10.1038","volume":"8","author":[{"given":"Lauren J","family":"Maskell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kashif","family":"Qamar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aram A","family":"Babakr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A","family":"Hawkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J","family":"Heads","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishwanie S","family":"Budhram-Mahadeo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,6,8]]},"reference":[{"key":"BFcddis2017185_CR1","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1146\/annurev.physiol.68.040104.113828","volume":"68","author":"KL Clark","year":"2006","unstructured":"Clark KL, Yutzey KE, Benson DW . 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