转录因子GATA4与原始心管的形成和静脉端的发育

GATA4 expression during primary heart tube formation and venous pole development of the mouse embryonic heart

目的：探讨GATA4表达和原始心管形成及心静脉端发育的关系。方法：用抗转录因子GATA4、抗α-平滑肌肌动蛋白（α-SMA）、抗α-横纹肌肌节肌动蛋白（α-SCA）、抗心肌肌球蛋白重链（MHC）抗体，对胎龄7．5～12d小鼠胚胎心连续切片进行免疫组织化学PAP法显色。结果：GATA4在7．5d小鼠胚胎生心板及原始心管呈较强表达，少数细胞显较弱MHC、α-SCA表达，α-SMA表达阴性。胎龄8．5d，第2生心区来源的胚胎心流出道和静脉端明显可辨，强α-SMA表达延伸至流出道、静脉端与心包腔脏壁中胚层的返折处，GATA4和MHC的表达主要集中在“S”型心的左、右心室，随发育逐渐向流出道和静脉端远侧延伸，但GATA4表达先于MHC和mSCA。胎龄9．5d后，静脉窦的形态发生以及窦壁心肌化在并入右心房的过程中逐渐完成。第11天，近右心房的上主静脉壁间充质增生分化形成GATA4和α-SMA阳性的窦房结原基，第12天获得较强MHC表达。间充质细胞向心肌细胞的分化在右下主静脉壁也可见到。结论：GATA4是原始生心区心肌前体细胞向心肌细胞分化的较早的标志蛋白。α-SMA是第2生心区来源的心肌细胞早期分化的标志蛋白，它的表达可能不受GATA4调节。GATA4主要调节定向后心肌细胞的增生和分化以及心管静脉端的正确成襻。

Objective： To investigate the relationship of GATA4 expression with the formation of primary heart tube and venous pole development of the mouse embryonic heart.Methods： Serial sections of embryonic day （El3） 7. 5-12 mouse hearts were stained with antibodies against transcriptional factor GATA4, α-smooth muscle actin （a-SMA）, α-sareomeric aetin （α- SCA） and myosin heavy chain （MHC）. Results： Strong expression of GATA 4 in the cardiogenie plate and fusing heart tube at ED 7. 5 was detected preceding that of MHC and α-SCA which were weakly expressed in a few cells, whereas α-SMA expression was still negative. At ED 8. 5, the outflow tract and venous pole originated from the second heart field were recognized dearly. Strong expression of α-SMA was seen extending to the distal ends of the outflow tract and venous pole at the reflection with splanchnic epithelium on the dorsal wall of the pericardial cavity whereas GATA 4 and MHC expression was mainly concentrated on the left and right ventricles of ＂S＂-shaped heart. Gradual extension of GATA 4 expression towards the distal ends of-the outflow tract and venous pole was seen at the late stage, and was always in advance of MHC and α-SCA expression. Morphogenesis and myocardialization of sinus venosus took place after ED 9.5 during which sinus venosus was incorporating into the right atrium. The GATA 4 and α-SMA positive anlage of sinoatrial node was found at ED 11 in the wall of the superior right cardinal vein close to the right atrium due to proliferation of mesenchymal cells, and at ED 12, began to show strong expression of MHC. Differentiation of mesenehymal cells into cardiomyocytes could also be detected in the walt of the inferior right cardinal vein. Conclusion： GATA 4 is an early marker indicating differentiation of cardioblast towards cardiomyocytes in the primary heart field. α-SMA is a marker indicating early differentiation of cardiomyocyte from the second heart field, and its expression during heart development is probably not regulated by GATA 4. GATA 4 might mainly regulate proliferation and further differentiation of committed cardiomyocytes and normal looping morphogenesis of the developing heart.