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Myocardial Differentiation is Dependent upon Endocardial Signaling During Early Cardiogenesis in vitro

Research output: Contribution to journalArticle

Leshana Saint-Jean, Nikolaos Barkas, Cristina Harmelink, Kevin L. Tompkins, Rebecca J Oakey, H. Scott Baldwin

Original languageEnglish
Article numberdev172619
JournalDevelopment
Volume146
Issue number9
Early online date8 May 2019
DOIs
Publication statusPublished - 8 May 2019

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Abstract

The endocardium interacts with the myocardium to promote proliferation and morphogenesis during the later stages of heart development. However, the role of the endocardium in early cardiac ontogeny remains under-explored. Given the shared origin, subsequent juxtaposition, and essential cell-cell interactions of endocardial and myocardial cells throughout heart development, we hypothesized that paracrine signaling from the endocardium to the myocardium is critical for initiating early differentiation of myocardial cells. To test this, we generated an in vitro, endocardial-specific ablation model using the diphtheria toxin receptor under the regulatory elements of the NFATc1 genomic locus (NFATc1-DTR). Early treatment of NFATc1-DTR embryoid bodies with diphtheria toxin efficiently ablated endocardial cells, which significantly attenuated the percent of beating EBs in culture and expression of early and late myocardial differentiation markers. The addition of Bmp2 during endocardial ablation partially rescued myocyte differentiation, maturation and function. Therefore, we conclude that early stages of myocardial differentiation rely on endocardial paracrine signaling mediated in part by Bmp2. Our findings provide novel insight into early endocardial-myocardial interactions that can be explored to promote early myocardial development and growth.

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