Abstract：
During heart development, the embryonic ventricle becomes enveloped by the epicardium, which adheres to the outer apical surface of the heart. This is concomitant with onset of ventricular trabeculation, where a subset of cardiomyocytes lose apicobasal polarity and delaminate basally from the ventricular wall. Llgl1 regulates the formation of apical cell junctions and apicobasal polarity, and we investigated its role in ventricular wall maturation. We found that llgl1 mutant zebrafish embryos exhibit aberrant apical extrusion of ventricular cardiomyocytes. While investigating apical cardiomyocyte extrusion, we identified a basal-to-apical shift in laminin deposition from the internal to the external ventricular wall. We find that epicardial cells express several laminin subunits as they adhere to the ventricle, and that the epicardium is required for laminin deposition on the ventricular surface. In llgl1 mutants, timely establishment of the epicardial layer is disrupted due to delayed emergence of epicardial cells, resulting in delayed apical deposition of laminin on the ventricular surface. Together, our analyses reveal an unexpected role for Llgl1 in correct timing of epicardial development, supporting integrity of the ventricular myocardial wall.
摘要：
在心脏发育过程中,胚胎心室被心外膜包围，它附着在心脏的外顶端表面。这伴随着心室小梁的发作，其中，一部分心肌细胞失去顶端的极性，并从心室壁基底脱层。Llgl1调节根尖细胞连接和根尖囊极性的形成，我们研究了它在心室壁成熟中的作用。我们发现llgl1突变斑马鱼胚胎表现出心室心肌细胞的异常顶端挤压。在研究心尖心肌细胞挤压时，我们发现层粘连蛋白沉积从心室壁内部向心尖转移.我们发现心外膜细胞表达几个层粘连蛋白亚基，层粘连蛋白沉积在心室表面需要心外膜。在llgl1突变体中，由于心外膜细胞的延迟出现，心外膜层的及时建立被破坏，导致层粘连蛋白在心室表面的延迟心尖沉积。一起,我们的分析揭示了Llgl1在心外膜发育的正确时机中的意想不到的作用，支持心室心肌壁的完整性。
