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Background: Proper coronary vasculature development is essential for late‐embryonic and adult heart function. The developmental regulation of coronary embryogenesis is complex and includes the coordinated activity of multiple signaling pathways. CCBE1 plays an important role during lymphangiogenesis, enhancing VEGF‐C signaling, which is also required for coronary vasculature formation. However, whether CCBE1 plays a similar role during coronary vasculature development is still unknown. Here, we investigate the coronary vasculature development in Ccbe1 mutant embryos. Results: We show that Ccbe1 is expressed in the epicardium, like Vegf‐c, and also in the sinus venosus (SV) at the stages of its contribution to coronary vasculature formation. We also report that absence of CCBE1 in cardiac tissue inhibited coronary growth that sprouts from the SV endocardium at the dorsal cardiac wall. This disruption of coronary formation correlates with abnormal processing of VEGF‐C propeptides, suggesting VEGF‐C–dependent signaling alteration. Moreover, Ccbe1 loss‐of‐function leads to the development of defective dorsal and ventral intramyocardial vessels. We also demonstrate that Ccbe1 mutants display delayed and mispatterned coronary artery (CA) stem formation. Conclusions: CCBE1 is essential for coronary vessel formation, independent of their embryonic origin, and is also necessary for peritruncal vessel growth and proper CA stem patterning. Developmental Dynamics 247:1135‐1145, 2018. © 2018 Wiley Periodicals, Inc. Key Findings: Ccbe1 is expressed in the epicardium and sinus venosus (SV) myocardium during coronary vasculature development.CCBE1 is required for SV endocardium‐derived coronary vessel development enhancing VEGF‐C processing.CCBE1 is required for the development of the coronary vessels forming at the ventral cardiac side of the heart.CCBE1 is necessary for peritruncal vessel growth and proper coronary artery (CA) stem formation. [ABSTRACT FROM AUTHOR]

Background: During the final stages of heart development the myocardium grows and becomes vascularized by means of paracrine factors and cell progenitors derived from the epicardium. There is evidence to suggest that retinoic acid (RA), a metabolite of vitamin A, plays an important role in epicardial‐based developmental programming. However, the consequences of altered RA‐signaling in coronary development have not been systematically investigated. Results: We explored the developmental consequences of altered RA‐signaling in late cardiogenic events that involve the epicardium. For this, we used a model of embryonic RA excess based on mouse embryos deficient in the retinaldehyde reductase DHRS3, and a complementary model of embryonic RA deficiency based on pharmacological inhibition of RA synthesis. We found that alterations in embryonic RA signaling led to a thin myocardium and aberrant coronary vessel formation and remodeling. Both excess, and deficient RA‐signaling are associated with reductions in ventricular coverage and density of coronary vessels, altered vessel morphology, and impaired recruitment of epicardial‐derived mural cells. Using a combined transcriptome and proteome profiling approach, we found that RA treatment of epicardial cells influenced key signaling pathways relevant for cardiac development. Conclusions: Epicardial RA‐signaling plays critical roles in the development of the coronary vasculature needed to support myocardial growth. Developmental Dynamics 247:976‐991, 2018. © 2018 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Coelomic cavities of vertebrates are lined by a mesothelium which develops from the lateral plate mesoderm. During development, the coelomic epithelium is a highly active cell layer, which locally is able to supply mesenchymal cells that contribute to the mesodermal elements of many organs and provide signals which are necessary for their development. The relevance of this process of mesenchymal cell supply to the developing organs is becoming clearer because genetic lineage tracing techniques have been developed in recent years. Body wall, heart, liver, lungs, gonads, and gastrointestinal tract are populated by cells derived from the coelomic epithelium which contribute to their connective and vascular tissues, and sometimes to specialized cell types such as the stellate cells of the liver, the Cajal interstitial cells of the gut or the Sertoli cells of the testicle. In this review we collect information about the contribution of coelomic epithelium derived cells to visceral development, their developmental fates and signaling functions. The common features displayed by all these processes suggest that the epithelial-mesenchymal transition of the embryonic coelomic epithelium is an underestimated but key event of vertebrate development, and probably it is shared by all the coelomate metazoans. Developmental Dynamics 245:307-322, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]