ABSTRACT
Objective To explore the mechanism underlying the rapid shortening of outflow tract and the formation of the right ventricle of the embryonic mouse heart .Methods Serial sections of embryonic mouse hearts from embryonic day 9 (E9) to E12(3 to 5 embryos for each stage)were stained with antibodies against α-sarcomeric actin (SCA), α-smooth muscle actin (SMA), GATA-4, myosin heavy chain (MHC), proliferating cell nuclear antigen (PCNA) or active caspase-3 (CAS-3).Results At E11, the aortic sac and the distal border of cardiac outflow tract had regressed towards the ventricle into the pericardial cavity , while GATA-4、SCA and SMA staining showed that precursors from the second heart field were differentiating into cardiomyocytes adding to the arterial pole of the heart to lengthen the outflow tract .The length of outflow tract rapidly shortened at E12.Before and during its shortening , no CAS-3 positive cell was detected in the entire outflow tract.During E10-12, the cardiomyocytes in the right ventricle and proximal outflow tract wall proliferated inward to form trabeculae, with some trabeculae extending into the ridges .Proximal extremities of the outflow tract ridges were gradually myocardialized remodeling into the trabeullar right ventricle wall .At E12, scattered SCA and SMA staining cells and SCA and SMA weak positive mesenchymal cell clusters , which were continuous with the outflow tract myocardium were detected in the mesenchymal proximal outflow tract ridges .These results suggested that the proximal outflow tract was remodeled into the right ventricle by trabecularization , during which mesenchymal ridges were trabecularlly myocardialized . Conclusion Ventricularization of the proximal outflow tract contributes to the trabecular right ventricle and resultes in the vapid shortening of outflow tract in the mouse embryonic heart .Cardiomyocyte appoptosis and transdifferentiation are found to play a more limited contribution during this process .
ABSTRACT
Objective To investigate the early development of the sinus venosus and the cardiac conduction system (CCS) of human embryonic hearts. Methods Serial transverse sections of 29 human embryonic hearts from Carnegie stage 10 to Carnegie stage 16 (C10-C16) were stained immunohistochemically with antibodies against α-smooth muscle actin(α-SMA),α-sarcomeric actin(α-SCA) and desmin ( DES ). Results During C12 and C13, the sinus venosus formed by confluence of systematic veins at the caudal end of the pericardial cavity could be recognized in the mesenchyme of primitive transverse septum. The mesenchymal cells of the sinus venosus gradually differentiated into α-SCA positive cardiocyocytes. At C14, the sinus venosus was within the pericardial cavity due to expansion of the pericardial cavity and incorporated into the right atrium. Differentiation of DES positive conductive cardiomyocyte was initiated in the right wall of atrio-ventricular canal of C10 embryonic heart and with the development, extended towards the myocardium of the interventricular sulcus to form His bundle, left and right bundle branches as well as the ventricular trabecular myocardium. In the atium, the strong expression of DES was first detected in the dorsal wall of C11 atrium. At C13, unique myocardial band showing α-SCA, α-SMA and DES expression in the left dorsal wall of the sinus venosus were found to be continuous with the basal wall of left atium and the dorsal wall of the atrio-ventricular canal, this band might be related to the development of conduction system from sinoatrial node to atrio-ventricular canal. During C14 to C16, primary conduction pathway of atria with strong DES expression was formed that extended from sinoatrial node along venous valves, DES positive myocardium in the dorsal and ventral walls of the atria to the right atrio-ventricular canal, respectively. Conclusions The mesenchyme of the primitive transverse septum is the heart forming field of human embryos responsible for formation of sinus venosus myocardium, cardiomyocytes are differentiated from mesenchymal cells in the primitive transverse septum and progressively added to the venous pole of the heart tube to form myocardial sinus venosus. The differentiation of CCS of the early human embryo initiates in the atrio-ventricular canal and develops gradually towards the arterial and venous poles of the heart tube. By C16, DES positive embryonic CCS can be clearly recognized morphologically.