Baldwin H S, Shen H M, Yan H C, DeLisser H M, Chung A, Mickanin C, Trask T, Kirschbaum N E, Newman P J, Albelda S M
Department of Pediatrics, Children's Hospital of Philadelphia, PA 19104.
Development. 1994 Sep;120(9):2539-53. doi: 10.1242/dev.120.9.2539.
The establishment of the cardiovascular system represents an early, critical event essential for normal embryonic development. An important component of vascular ontogeny is the differentiation and development of the endothelial and endocardial cell populations. This involves, at least in part, the expression and function of specific cell surface receptors required to mediate cell-cell and cell-matrix adhesion. Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) may well serve such a function. It is a member of the immunoglobulin superfamily expressed by the entire vascular endothelium in the adult. It is capable of mediating adhesion by a heterophilic mechanism requiring glycosaminoglycans, as well as by a homophilic, glycosaminoglycan independent, mechanism. It has been shown to regulate the expression of other adhesion molecules on naive T cells. This report documents by RT-PCR and immunohistochemical analysis the expression of PECAM-1 during early post implantation mouse embryo development. PECAM-1 was expressed by early endothelial precursors first within the yolk sac and subsequently within the embryo itself. Interestingly, embryonic PECAM-1 was expressed as multiple isoforms in which one or more clusters of polypeptides were missing from the cytoplasmic domain. The sequence and location of the deleted polypeptides corresponded to exons found in the human PECAM-1 gene. The alternatively spliced isoforms were capable of mediating cell-cell adhesion when transfected into L-cells. The isoforms differed, however, in their sensitivity to a panel of anti-PECAM-1 monoclonal antibodies. These data suggest that changes in the cytoplasmic domain of PECAM-1 may affect its function during cardiovascular development, and are consistent with our earlier report that systematic truncation of the cytoplasmic domain of human PECAM-1 resulted in changes in its ligand specificity, divalent cation and glycosaminoglycan dependence, as well as its susceptibility to adhesion blocking monoclonal antibodies. This is the first report of naturally occurring alternatively spliced forms of PECAM-1 having possible functional implications.
心血管系统的建立是正常胚胎发育早期至关重要的事件。血管个体发生的一个重要组成部分是内皮细胞和心内膜细胞群体的分化与发育。这至少部分涉及介导细胞间和细胞与基质粘附所需的特定细胞表面受体的表达和功能。血小板内皮细胞粘附分子-1（PECAM-1，CD31）很可能具有这样的功能。它是免疫球蛋白超家族的成员，在成体中由整个血管内皮表达。它能够通过需要糖胺聚糖的异嗜性机制以及通过同源性、不依赖糖胺聚糖的机制介导粘附。已表明它可调节未成熟T细胞上其他粘附分子的表达。本报告通过逆转录聚合酶链反应（RT-PCR）和免疫组织化学分析记录了PECAM-1在植入后早期小鼠胚胎发育过程中的表达。PECAM-1首先在卵黄囊内由早期内皮前体细胞表达，随后在胚胎自身内表达。有趣的是，胚胎PECAM-1以多种异构体形式表达，其中一个或多个多肽簇在细胞质结构域中缺失。缺失多肽的序列和位置与人类PECAM-1基因中的外显子相对应。当转染到L细胞中时，这些可变剪接的异构体能够介导细胞间粘附。然而，这些异构体对一组抗PECAM-1单克隆抗体的敏感性不同。这些数据表明，PECAM-1细胞质结构域的变化可能会影响其在心血管发育过程中的功能，这与我们早期的报告一致，即人类PECAM-1细胞质结构域的系统性截短导致其配体特异性、二价阳离子和糖胺聚糖依赖性以及对粘附阻断单克隆抗体的敏感性发生变化。这是关于具有可能功能意义的天然存在的PECAM-1可变剪接形式的首次报告。
