Tsuda T, Philp N, Zile M H, Linask K K
Division of Cardiology, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine 19104, USA.
Dev Biol. 1996 Jan 10;173(1):39-50. doi: 10.1006/dbio.1996.0005.
The early embryo is initially bilaterally symmetrical. One of the first distinct indications of asymmetry in the embryo occurs during heart looping. The midline tubular heart begins to bend to the right to form a C-shaped structure around 30 hr of development in the avian model. A molecular basis for heart asymmetry and direction of looping is not known, although factors inherent to the myocardium are believed to underlie looping. A left-right asymmetric localization of a specific molecule in the bilateral heart forming regions has not been reported previously. One molecule that we are calling flectin (flectere, in L., to bend or to loop) shows a bilateral asymmetric localization early in the heart forming mesoderm and continues to be expressed asymmetrically in a highly organized manner in the cardiac jelly during heart looping. This large extracellular matrix molecule has been identified using a monoclonal antibody F-22 (Mieziewska et al., 1994a,b). Flectin shows a discrete spatiotemporal pattern of extracellular matrix expression during avian heart development. An asymmetric expression of flectin is observed during heart development at stage 7+/8- (approximately at 24 hr of development around the 3-somite stage). It is predominantly expressed in the left precardiac mesoderm at this developmental period. Between stages 12 and 14, flectin continues to be asymmetrically expressed in the myocardium and is localized at high levels on the basal side of the myocardium and within the cardiac jelly extending to the endocardial cell surfaces. In the same plane of the looping part of the heart it is differentially organized within the cardiac jelly on the convex side and in the outer loop areas. A reduced expression is apparent anteriorly and posteriorly along the tubular heart. The initial asymmetry of localization is maintained throughout the tubular heart. At stage 22 (Embryonic Day 3.5), intensity of immunolocalization of flectin is significantly decreased, with left-right asymmetry becoming less discernible or absent. It again is expressed in Day 10 embryonic hearts. Flectin expression appears to be modulated by retinoids. In vitamin A-deficient quail embryonic hearts that do not loop (Dersch and Zile, 1993; Twal et al., 1995), flectin protein expression is decreased and disorganized, as are other extracellular matrix components comprising the cardiac jelly.
早期胚胎最初是双侧对称的。胚胎中不对称的最早明显迹象之一发生在心脏成环过程中。在鸟类模型中，发育约30小时时，中线管状心脏开始向右弯曲形成C形结构。尽管人们认为心肌固有的因素是心脏成环的基础，但心脏不对称和成环方向的分子基础尚不清楚。此前尚未报道过特定分子在双侧心脏形成区域的左右不对称定位。我们称为flectin（源自拉丁语flectere，意为弯曲或成环）的一种分子在心脏形成中胚层早期表现出双侧不对称定位，并在心脏成环过程中继续以高度有组织的方式在心脏胶中不对称表达。这种大的细胞外基质分子已通过单克隆抗体F-22鉴定出来（Mieziewska等人，1994a，b）。Flectin在鸟类心脏发育过程中表现出离散的时空模式的细胞外基质表达。在第7+/8-阶段（约在3体节阶段发育24小时左右）的心脏发育过程中观察到flectin的不对称表达。在此发育阶段，它主要在左心前中胚层表达。在第12至14阶段之间，flectin继续在心肌中不对称表达，并高水平定位在心肌的基侧以及延伸至心内膜细胞表面的心脏胶内。在心脏成环部分的同一平面中，它在心脏胶的凸侧和外环区域内有差异地组织。沿管状心脏的前部和后部表达明显减少。定位的初始不对称在整个管状心脏中保持。在第22阶段（胚胎第3.5天），flectin的免疫定位强度显著降低，左右不对称变得不太明显或消失。它在第10天的胚胎心脏中再次表达。Flectin的表达似乎受类视黄醇调节。在未发生成环的维生素A缺乏鹌鹑胚胎心脏中（Dersch和Zile，1993；Twal等人，1995），flectin蛋白表达减少且无序，构成心脏胶的其他细胞外基质成分也是如此。
