CDC42 is required for epicardial and pro-epicardial development by mediating FGF receptor trafficking to the plasma membrane.

Autor:	Li J; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA., Miao L; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA.; Institute of Translational Medicine, Nanchang University, Nanchang 330031, China.; School of Life Sciences, Nanchang University, Nanchang 330031, China., Zhao C; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA., Shaikh Qureshi WM; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA., Shieh D; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA., Guo H; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA., Lu Y; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA., Hu S; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA., Huang A; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA., Zhang L; Developmental and Regenerative Biology, Mount Sinai Hospital, New York, NY 10029, USA., Cai CL; Developmental and Regenerative Biology, Mount Sinai Hospital, New York, NY 10029, USA., Wan LQ; Department of Biomedical Engineering, Rensselaer Polytechnic Institute, 110 8th street, Biotech 2147, Troy, NY 12180, USA., Xin H; Institute of Translational Medicine, Nanchang University, Nanchang 330031, China.; School of Life Sciences, Nanchang University, Nanchang 330031, China., Vincent P; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA., Singer HA; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA., Zheng Y; Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA., Cleaver O; Molecular Biology, UT Southwestern, Dallas, TX 75390, USA., Fan ZC; International Collaborative Research Center for Health Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China., Wu M; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA wum@mail.amc.edu.
Jazyk:	angličtina
Zdroj:	Development (Cambridge, England) [Development] 2017 May 01; Vol. 144 (9), pp. 1635-1647.
DOI:	10.1242/dev.147173
Abstrakt:	The epicardium contributes to multiple cardiac lineages and is essential for cardiac development and regeneration. However, the mechanism of epicardium formation is unclear. This study aimed to establish the cellular and molecular mechanisms underlying the dissociation of pro-epicardial cells (PECs) from the pro-epicardium (PE) and their subsequent translocation to the heart to form the epicardium. We used lineage tracing, conditional deletion, mosaic analysis and ligand stimulation in mice to determine that both villous protrusions and floating cysts contribute to PEC translocation to myocardium in a CDC42-dependent manner. We resolved a controversy by demonstrating that physical contact of the PE with the myocardium constitutes a third mechanism for PEC translocation to myocardium, and observed a fourth mechanism in which PECs migrate along the surface of the inflow tract to reach the ventricles. Epicardial-specific Cdc42 deletion disrupted epicardium formation, and Cdc42 null PECs proliferated less, lost polarity and failed to form villous protrusions and floating cysts. FGF signaling promotes epicardium formation in vivo , and biochemical studies demonstrated that CDC42 is involved in the trafficking of FGF receptors to the cell membrane to regulate epicardium formation. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2017. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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