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Publication : Coronary Artery Formation Is Driven by Localized Expression of R-spondin3.

First Author  Da Silva F Year  2017
Journal  Cell Rep Volume  20
Issue  8 Pages  1745-1754
PubMed ID  28834739 Mgi Jnum  J:254209
Mgi Id  MGI:6104150 Doi  10.1016/j.celrep.2017.08.004
Citation  Da Silva F, et al. (2017) Coronary Artery Formation Is Driven by Localized Expression of R-spondin3. Cell Rep 20(8):1745-1754
abstractText  Coronary arteries are essential to support the heart with oxygen, and coronary heart disease is one of the leading causes of death worldwide. The coronary arteries form at highly stereotyped locations and are derived from the primitive vascular plexus of the heart. How coronary arteries are remodeled and the signaling molecules that govern this process are poorly understood. Here, we have identified the Wnt-signaling modulator Rspo3 as a crucial regulator of coronary artery formation in the developing heart. Rspo3 is specifically expressed around the coronary stems at critical time points in their development. Temporal ablation of Rspo3 at E11.5 leads to decreased beta-catenin signaling and a reduction in arterial-specific proliferation. As a result, the coronary stems are defective and the arterial tree does not form properly. These results identify a mechanism through which localized expression of RSPO3 induces proliferation of the coronary arteries at their stems and permits their formation.
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