Structural Biophysics Group, School of Optometry & Vision Sciences, Cardiff University, Maindy Road, Cathays, Cardiff CF24 4HQ, UK.
School of Biosciences, Cardiff University, Sir Martin Evans Building, Museum Avenue, Cardiff CF10 3AX, UK.
Int J Mol Sci. 2023 Feb 10;24(4):3555. doi: 10.3390/ijms24043555.
The cornea forms the tough and transparent anterior part of the eye and by accurate shaping forms the major refractive element for vision. Its largest component is the stroma, a dense collagenous connective tissue positioned between the epithelium and the endothelium. In chicken embryos, the stroma initially develops as the primary stroma secreted by the epithelium, which is then invaded by migratory neural crest cells. These cells secrete an organised multi-lamellar collagenous extracellular matrix (ECM), becoming keratocytes. Within individual lamellae, collagen fibrils are parallel and orientated approximately orthogonally in adjacent lamellae. In addition to collagens and associated small proteoglycans, the ECM contains the multifunctional adhesive glycoproteins fibronectin and tenascin-C. We show in embryonic chicken corneas that fibronectin is present but is essentially unstructured in the primary stroma before cell migration and develops as strands linking migrating cells as they enter, maintaining their relative positions as they populate the stroma. Fibronectin also becomes prominent in the epithelial basement membrane, from which fibronectin strings penetrate into the stromal lamellar ECM at right angles. These are present throughout embryonic development but are absent in adults. Stromal cells associate with the strings. Since the epithelial basement membrane is the anterior stromal boundary, strings may be used by stromal cells to determine their relative anterior-posterior positions. Tenascin-C is organised differently, initially as an amorphous layer above the endothelium and subsequently extending anteriorly and organising into a 3D mesh when the stromal cells arrive, enclosing them. It continues to shift anteriorly in development, disappearing posteriorly, and finally becoming prominent in Bowman's layer beneath the epithelium. The similarity of tenascin-C and collagen organisation suggests that it may link cells to collagen, allowing cells to control and organise the developing ECM architecture. Fibronectin and tenascin-C have complementary roles in cell migration, with the former being adhesive and the latter being antiadhesive and able to displace cells from their adhesion to fibronectin. Thus, in addition to the potential for associations between cells and the ECM, the two could be involved in controlling migration and adhesion and subsequent keratocyte differentiation. Despite the similarities in structure and binding capabilities of the two glycoproteins and the fact that they occupy similar regions of the developing stroma, there is little colocalisation, demonstrating their distinctive roles.
角膜形成眼球坚韧透明的前部，通过精确的形状形成主要的屈光元件用于视力。其最大的组成部分是基质，是一种位于上皮细胞和内皮细胞之间的致密胶原结缔组织。在鸡胚中，基质最初由上皮细胞分泌的初级基质形成，然后被迁移的神经嵴细胞侵入。这些细胞分泌有组织的多层胶原细胞外基质 (ECM)，成为角膜细胞。在单个层片中，胶原原纤维平行排列，在相邻的层片中约呈正交取向。除了胶原和相关的小蛋白聚糖外，ECM 还包含多功能黏附糖蛋白纤连蛋白和 tenascin-C。我们在鸡胚角膜中表明，纤连蛋白存在，但在细胞迁移前的初级基质中基本上没有结构，并且随着进入基质的迁移细胞形成链而发展，在填充基质时保持它们的相对位置。纤连蛋白也在上皮细胞基底膜中变得明显，纤连蛋白链从基底膜中以直角穿透到基质层状 ECM 中。这些在整个胚胎发育过程中都存在，但在成人中不存在。基质细胞与这些链相连。由于上皮细胞基底膜是前基质边界，因此基质细胞可能会使用这些链来确定它们的相对前后位置。Tenascin-C 的组织方式不同，最初在上皮细胞上方呈无定形层，随后向前延伸，并在基质细胞到达时组织成 3D 网格，将其包围。在发育过程中，它继续向前移动，向后消失，最后在上皮细胞下方的 Bowman 层变得明显。Tenascin-C 和胶原组织的相似性表明，它可能将细胞与胶原连接起来，使细胞能够控制和组织发育中的 ECM 结构。纤连蛋白和 tenascin-C 在细胞迁移中具有互补作用，前者具有黏附性，后者具有抗黏附性，并能够将细胞从与纤连蛋白的黏附中置换出来。因此，除了细胞与 ECM 之间可能存在的关联外，这两种物质还可能参与控制迁移和黏附以及随后的角膜细胞分化。尽管这两种糖蛋白在结构和结合能力上有相似之处，并且它们占据了发育中基质的相似区域，但它们的共定位很少，这表明它们具有独特的作用。
