Endocardium differentiation through Sox17 expression in endocardium precursor cells regulates heart development in mice
Author
Saba, RieKitajima, Keiko
Rainbow, Lucille
Engert, Silvia
Uemura, Mami
Ishida, Hidekazu
Kokkinopoulos, Ioannis
Shintani, Yasunori
Miyagawa, Shigeru
Kanai, Yoshiakira
Kanai-Azuma, Masami
Koopman, Peter
Meno, Chikara
Kenny, John
Lickert, Heiko
Saga, Yumiko
Suzuki, Ken
Sawa, Yoshiki
Yashiro, Kenta
Date
2019-08-16
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Saba, R., Kitajima, K., Rainbow, L., Engert, S., Uemura, M., Ishida, H., Kokkinopoulos, I., Shintani, Y., Miyagawa, S., Kanai, Y., Kanai-Azuma, M., Koopman, P., Meno, C., Kenny, J., Lickert, H., Saga, Y., Suzuki, K., Sawa, Y. and Yashiro, K. Endocardium differentiation through Sox17 expression in endocardium precursor cells regulates heart development in mice. Scientific Reports, 2019, 9(1). doi: https://doi.org/10.1038/s41598-019-48321-yAbstract
The endocardium is the endothelial component of the vertebrate heart and plays a key role in heart development. Where, when, and how the endocardium segregates during embryogenesis have remained largely unknown, however. We now show that Nkx2-5+ cardiac progenitor cells (CPCs) that express the Sry-type HMG box gene Sox17 from embryonic day (E) 7.5 to E8.5 specifically differentiate into the endocardium in mouse embryos. Although Sox17 is not essential or sufficient for endocardium fate, it can bias the fate of CPCs toward the endocardium. On the other hand, Sox17 expression in the endocardium is required for heart development. Deletion of Sox17 specifically in the mesoderm markedly impaired endocardium development with regard to cell proliferation and behavior. The proliferation of cardiomyocytes, ventricular trabeculation, and myocardium thickening were also impaired in a non-cell-autonomous manner in the Sox17 mutant, likely as a consequence of down-regulation of NOTCH signaling. An unknown signal, regulated by Sox17 and required for nurturing of the myocardium, is responsible for the reduction in NOTCH-related genes in the mutant embryos. Our results thus provide insight into differentiation of the endocardium and its role in heart development.Funder
Medical Research Council, U.K.; British Heart Foundation; Japan Society for the Promotion of Science Grants-in-Aid for Scientific ResearchGrant Number
G0900105; PG/11/102/29213; 17H04228; 17K08490ae974a485f413a2113503eed53cd6c53
10.1038/s41598-019-48321-y
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