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In mouse, <jats:italic>Cited2<\/jats:italic> is necessary for embryogenesis, particularly for heart development, and its depletion in embryonic stem cells (ESC) impairs cardiac differentiation. We have now determined that <jats:italic>Cited2<\/jats:italic> depletion in ESC affects the expression of transcription factors and cardiopoietic genes involved in early mesoderm and cardiac specification. Interestingly, the supplementation of the secretome prepared from ESC overexpressing CITED2, during the onset of differentiation, rescued the cardiogenic defects of <jats:italic>Cited2<\/jats:italic>-depleted ESC. In addition, we demonstrate that the proteins WNT5A and WNT11 held the potential for rescue. We also validated the zebrafish as a model to investigate <jats:italic>cited2<\/jats:italic> function during development. Indeed, the microinjection of morpholinos targeting <jats:italic>cited2<\/jats:italic> transcripts caused developmental defects recapitulating those of mice knockout models, including the increased propensity for cardiac defects and severe death rate. Importantly, the co-injection of anti-<jats:italic>cited2<\/jats:italic> morpholinos with either CITED2 or WNT5A and WNT11 recombinant proteins corrected the developmental defects of Cited2-morphants. This study argues that defects caused by the dysfunction of <jats:italic>Cited2<\/jats:italic> at early stages of development, including heart anomalies, may be remediable by supplementation of exogenous molecules, offering the opportunity to develop novel therapeutic strategies aiming to prevent CHD.<\/jats:p>","DOI":"10.1038\/s41419-019-1816-6","type":"journal-article","created":{"date-parts":[[2019,8,4]],"date-time":"2019-08-04T23:02:21Z","timestamp":1564959741000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Exogenous WNT5A and WNT11 proteins rescue CITED2 dysfunction in mouse embryonic stem cells and zebrafish morphants"],"prefix":"10.1038","volume":"10","author":[{"given":"Jo\u00e3o M. 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