小鼠胚胎心流出道近段心室化形成右心室小梁部
李海荣 杨艳萍 王晶晶 曹锡梅 刘慧霞 崔慧林 张涛 景雅*
解剖学报 ›› 2014, Vol. 45 ›› Issue (5) : 698-703.
小鼠胚胎心流出道近段心室化形成右心室小梁部
Ventricularization of the proximal cardiac outflow tract contributes to trabeculated right ventricle in mouse embryo
目的 探讨小鼠胚胎心流出道快速缩短及右心室形成机制。方法 用抗α-横纹肌肌动蛋白(SCA)、抗肌球蛋白重链(MHC)抗体标记心肌,抗GATA-4抗体标记心肌及其前体细胞,抗α-平滑肌肌动蛋白(SMA)抗体标记早期心肌细胞,抗增殖细胞核抗原(PCNA)抗体显示增殖细胞,抗人/鼠活性Caspase-3(CAS-3)抗体检测凋亡早期细胞,对胚龄9d(E9)~E12(不同胚龄胚胎各取3~5只)小鼠胚胎心连续切片行免疫组织化学染色。 结果 E11时动脉囊及流出道远端心肌界退却至心包腔内,GATA-4、SCA、SMA染色示第二生心区前体细胞不断分化为心肌细胞添加在心动脉端使流出道延长。小鼠胚胎心流出道于E12缩短,缩短前及缩短过程中全长未检测到CAS-3阳性细胞。E10~12时右心室及流出道近段心肌不断增生形成小梁并侵入邻近的流出道嵴内,流出道近端嵴逐渐小梁状心肌化改建为右心室壁;E12时近段间充质性流出道嵴内出现散在的SCA、SMA阳性心肌细胞及与流出道心肌相延续的SCA、SMA弱阳性心肌细胞流,这些结果表明近段流出道心肌小梁化、流出道嵴小梁状肌化形成了右心室小梁部。结论 小鼠胚胎流出道近段心室化致右心室小梁部形成及流出道快速缩短,心肌细胞凋亡及转分化对流出道快速缩短的作用甚微。
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.
胚胎;心流出道 / GATA-4 / α-横纹肌肌动蛋白 / α-平滑肌肌动蛋白 / 增殖细胞核抗原 / 免疫组织化学 / 小鼠
Embryo / Cardiac outflow tract / GATA-4 / α-Sarcomeric actin / α-Smooth muscle actin / Proliferating cell nuclear antigen / Immunohistochemistry / Mouse
[1]Watanabe M, Choudhry A, Berlan M, et al. Developmental remodeling and shortening of the cardiac outflow tract involves myocyte programmed cell death[J]. Development, 1998,125(19):3809-3820.
[2]Anderson RH, Webb S, Brown NA, et al. Development of the heart: (3) formation of the ventricular outflow tracts, arterial valves, and intrapericardial arterial trunks[J]. Heart, 2003,89(9): 1110-1118.
[3]Paul MH, Harvey RP, Wegner M, et al. Cardiac outflow tract development relies on the complex function of Sox4 and Sox11 in multiple cell types[J]. Cell Mol Life Sci, 2014, 71(15): 2931-2945.
[4]van den Hoff MJ, Moorman AF, Ruijter JM, et al. Myocardialization of the cardiac outflow tract[J]. Dev Biol, 1999,212(2):477-490.
[5]Anderson RH, Chaudhry B, Mohun TJ, et al. Normal and abnormal development of the intrapericardial arterial trunks in humans and mice[J]. Cardiovasc Res, 2012,95(1):108-115.
[6]Dor X, Corone P. Migration and torsions of the conotruncus in the chick embryo heart: observational evidence and conclusions drawn from experimental intervention[J]. Heart Vessels, 1985,1(4):195-211.
[7]de la Cruz MV, Sánchez Gómez C, Arteaga MM, et al. Experimental study of the development of the truncus and the conus in the chick embryo[J]. J Anat, 1977,123(Pt 3):661-686.
[8]Li HR, Li SY, Yang YP, et al. The development of the outflow tract in the early embryonic human heart[J]. Acta Anatomica sinica, 2008,39(3):400-405. (in Chinese)
李海荣,李素云,杨艳萍,等. 人胚胎早期心脏流出道的发育[J]. 解剖学报, 2008,39(3):400-405.
[9]Yang YP, Li HR, Jing Y. Septation and shortening of outflow tract in embryonic mouse heart involve changes in cardiomyocyte phenotype and alpha-SMA positive cells in the endocardium[J]. Chin Med J, 2004, 117(8):1240-1245.
[10]Ya J, van den Hoff MJ, de Boer PA, et al. Normal development of the outflow tract in the rat[J]. Circ Res, 1998,82(4):464-472.
[11]Goor DA, Dische R, Lillehei CW. The conotruncus. I. Its normal inversion and conus absorption[J]. Circulation, 1972,46(2):375-384.
[12]Rana MS, Horsten NC, Tesink-Taekema S, et al. Trabeculated right ventricular free wall in the chicken heart forms by ventricularization of the myocardium initially forming the outflow tract[J]. Circ Res, 2007,100(7):1000-1007.
[13]Sharma PR, Anderson RH, Copp AJ, et al. Spatiotemporal analysis of programmed cell death during mouse cardiac septation[J]. Anat Rec A Discov Mol Cell Evol Biol, 2004,277(2):355-369.
[14]Barbosky L, Lawrence DK, Karunamuni G, et al. Apoptosis in the developing mouse heart[J]. Dev Dyn, 2006,235(9):2592-2602.
[15]Verzi MP, McCulley DJ, De Val S, et al. The right ventricle, outflow tract, and ventricular septum comprise a restricted expression domain within the secondary/anterior heart field[J]. Dev Biol, 2005,287(1):134-145.
[16]Cai CL, Liang X, Shi Y, et al. Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart[J]. Dev Cell, 2003,5(6):877-889.
[17]Jin JZ, Tan M, Ding J. Analysis of cripto expression during mouse cardiac myocyte differentiation[J]. Int J Dev Biol, 2013,57(9-10):793-797.
[18]Watanabe Y, Buckingham M. The formation of the embryonic mouse heart: heart fields and myocardial cell lineages[J]. Ann N Y Acad Sci, 2010,1188(1):15-24.
[19]Evans SM, Yelon D, Conlon FL, et al. Myocardial lineage development[J]. Circ Res, 2010,107(12):1428-1444.
[20]Laugwitz KL, Moretti A, Caron L, et al. Islet1 cardiovascular progenitors: a single source for heart lineages[J]? Development, 2008,135(2):193-205.
[21]Zhao C, Guo H, Li J, et al. Numb family proteins are essential for cardiac morphogenesis and progenitor differentiation[J]. Development, 2014,141(2):281-295.
[22]Yang YP, Li HR, Jing Y, et al. Forming of myocardial septum in the proximal part of outflow tract in embryonic heart of mouse[J]. Chinese Journal of Anatomy, 2007,30(6) :698-701. (in Chinese)
杨艳萍,李海荣,景雅,等. 小鼠胚胎心脏流出道隔的形成机制[J]. 解剖学杂志, 2007,30(6):698-701.
[23]MeilhacMeilhac SM, Esner MEsner M, Kerszberg MKerszberg M, et al. Oriented clonal cell growth in the developing mouse myocardium underlies cardiac morphogenesis[J]. J Cell Biol, 2004,164(1):97-109.
[24]Franco D, Kelly R, Lamers WH, et al. Regionalized transcriptional domains of myosin light chain 3f transgenes in the embryonic mouse heart: morphogenetic implications[J]. Dev Biol, 1997,188(1):17-33.
人胚胎第二生心区和心脏流出道的发育;小鼠胚胎心背侧间充质突与心房发育;人胚胎第二生心区和心脏流出道的发育;小鼠胚胎心脏流出道发育过程中心肌细胞和心内膜α-SMA阳性细胞变化
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