The Role Of Sliw In The Development Of Mouse Embryonic Heart

Heart development is one of the first events during embryogenesis, including aseries of orderly processes such as the specialization of cardiac precursor cells, theformation and remodeling of four chambers, and the formation of heart valves. It is afine-tuned process regulated by the interplays of multiple signaling pathways. Wntsare secreted proteins, which activate intracellular signaling pathways by binding to themembrane receptors. Many studies have showed that Wnt signaling pathway plays animportant role in multiple stages of heart development, but whether and how do thedistinct cell type-derived Wnts play a different role during heart development islargely unknown.Sliw binds to Wnt proteins to assist Wnt secretion to extracellular space. It isrequired for the secretion of almost all Wnts in mammals. In this study, by using theCre-LoxP system we deleted Sliw gene specifically in the endothelial cells or in thesecond heart field myocardial cells, and systematically analyzed the phenotypes of thetwo kinds of mutant mice at whole-mount and histological levels. Endothelialcells-specific Sliw decifient mice died at embryonic day15.5due to multiple heartdefects. These defects included ventricular septal defect, outflow track defect,hypertrabeculation and ventricular noncompaction. Further studies showed that theproliferation of myocardial cells was increased in the trabeculae but not in thecompact layer, and the expression of extracellular matrix molecules was abnormal inthe mutant hearts. In addition, the second heart field-specific Sliw deleted miceshowed defects in the development of right ventriculae, and the proliferation ofmyocardial cells was decreased in the compact layer but not in the trabeculae. Insummary, Wnts derived from different cell types play different roles in the biologicalbehaviors of myocardial cells during embryogenesis, and Wnts secreted fromendocardial cells are required for the cardiac development and ventricle compaction.