Sheppard A M, Onken M D, Rosen G D, Noakes P G, Dean D C
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Cell Adhes Commun. 1994 Apr;2(1):27-43. doi: 10.3109/15419069409014200.
Interaction of alpha 4 integrins with vascular cell adhesion molecule-1 (VCAM-1) is classically important for immune function. However, we found recently that these receptors have a second role, in embryogenesis, where they mediate cell-cell interactions that are important for skeletal muscle differentiation. Here, we present evidence of an expanding role for these receptors in murine development. alpha 4 and VCAM-1 were found at embryonic sites of hematopoiesis, suggesting a role for these receptors during embryogenesis that parallels their hematopoietic function in adult bone marrow. During angiogenesis in the lung, alpha 4 and VCAM-1 were found on mesenchyme that gives rise to vascular endothelium and smooth muscle. alpha 4 persisted on the smooth muscle and the endothelium of newly forming vessels where it colocalized with its extracellular matrix ligand, fibronectin (FN). These patterns suggest several roles for alpha 4 integrins and their ligands in angiogenesis. alpha 4 was also found on neural crest derivatives where it colocalized with FN. alpha 4 was expressed selectively on cells in the dorsal root ganglia: it was apparent along ventral projections, but absent from dorsal projections, suggesting that alpha 4 integrins could be involved in defining neuronal fates. Although VCAM-1 was not expressed on most neural crest derivatives, it was found in the neural crest-derived outflow tract of the embryonic heart, where it colocalized with alpha 4. These results imply that alpha 4 integrins and their ligands could be important for migration or differentiation of neural crest. alpha 4 was also expressed on embryonic retina and FN was found on inductive mesenchyme surrounding the eye, suggesting a role for these proteins in eye development. Finally, based on their patterns of expression, we conclude that VCAM-1 only participates in a subset of interactions involving alpha 4 integrins, whereas FN appears to be the more general ligand.
α4整合素与血管细胞黏附分子-1（VCAM-1）的相互作用在免疫功能中具有经典的重要性。然而，我们最近发现这些受体还有第二个作用，即在胚胎发生过程中，它们介导对骨骼肌分化很重要的细胞间相互作用。在这里，我们提供证据表明这些受体在小鼠发育中的作用正在扩大。在胚胎造血部位发现了α4和VCAM-1，这表明这些受体在胚胎发生过程中的作用与其在成年骨髓中的造血功能相似。在肺血管生成过程中，在产生血管内皮和平滑肌的间充质上发现了α4和VCAM-1。α4持续存在于新形成血管的平滑肌和内皮上，并与其细胞外基质配体纤连蛋白（FN）共定位。这些模式表明α4整合素及其配体在血管生成中有多种作用。在神经嵴衍生物上也发现了α4，它与FN共定位。α4在背根神经节的细胞上选择性表达：在腹侧突起上明显，但在背侧突起上不存在，这表明α4整合素可能参与确定神经元命运。虽然VCAM-1在大多数神经嵴衍生物上不表达，但在胚胎心脏的神经嵴衍生流出道中发现了它，它与α4共定位。这些结果意味着α4整合素及其配体可能对神经嵴的迁移或分化很重要。α4在胚胎视网膜上也有表达，在眼睛周围的诱导性间充质上发现了FN，这表明这些蛋白质在眼睛发育中起作用。最后，根据它们的表达模式，我们得出结论，VCAM-1仅参与涉及α4整合素的一部分相互作用，而FN似乎是更普遍的配体。
