FRS2α-dependent cell fate transition during endocardial cushion morphogenesis.

Autor: Chen D; Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT, 06511, USA., Zhu X; Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT, 06511, USA., Kofler N; Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT, 06511, USA., Wang Y; Departments of Genetics, Pediatrics and Medicine (Cardiology), Wilf Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY, 10461, USA., Zhou B; Departments of Genetics, Pediatrics and Medicine (Cardiology), Wilf Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY, 10461, USA., Simons M; Department of Internal Medicine and Department of Cell Biology, Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT, USA. Electronic address: michael.simons@yale.edu.
Jazyk: angličtina
Zdroj: Developmental biology [Dev Biol] 2020 Feb 01; Vol. 458 (1), pp. 88-97. Date of Electronic Publication: 2019 Oct 25.
DOI: 10.1016/j.ydbio.2019.10.022
Abstrakt: Atrioventricular valve development requires endothelial-to-mesenchymal transition (EndMT) that induces cushion endocardial cells to give rise to mesenchymal cells crucial to valve formation. In the adult endothelium, deletion of the docking protein FRS2α induces EndMT by activating TGFβ signaling in a miRNA let-7-dependent manner. To study the role of endothelial FRS2α during embryonic development, we generated mice with an inducible endothelial-specific deletion of Frs2α (FRS2α iECKO ). Analysis of the FRS2α iECKO embryos uncovered a combination of impaired EndMT in AV cushions and defective maturation of AV valves leading to development of thickened, abnormal valves when Frs2α was deleted early (E7.5) in development. At the same time, no AV valve developmental abnormalities were observed after late (E10.5) deletion. These observations identify FRS2α as a pivotal controller of cell fate transition during both EndMT and post-EndMT valvulogenesis.
Competing Interests: Declaration of competing interest None.
(Copyright © 2019. Published by Elsevier Inc.)
Databáze: MEDLINE
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