PDF(Pubmed)
Abstract：
The role extracellular matrix (ECM) in multiple events of morphogenesis has been well described, little is known about its specific role in early eye development. One of the first morphogenic events in lens development is placodal thickening, which converts the presumptive lens ectoderm from cuboidal to pseudostratified epithelium. This process occurs in the anterior pre-placodal ectoderm when the optic vesicle approaches the cephalic ectoderm and is regulated by transcription factor Pax6 and secreted BMP4. Since cells and ECM have a dynamic relationship of interdependence and modulation, we hypothesized that the ECM evolves with cell shape changes during lens placode formation. This study investigates changes in optic ECM including both protein distribution deposition, extracellular gelatinase activity and gene expression patterns during early optic development using chicken and mouse models. In particular, the expression of Timp2, a metalloprotease inhibitor, corresponds with a decrease in gelatinase activity within the optic ECM. Furthermore, we demonstrate that optic ECM remodeling depends on BMP signaling in the placode. Together, our findings suggest that the lens placode plays an active role in remodeling the optic ECM during early eye development.
摘要：
细胞外基质（ECM）在多种形态发生事件中的作用已经得到了很好的描述，人们对它在早期眼部发育中的具体作用知之甚少。晶状体发育的第一个形态发生事件之一是胎盘增厚，将假定的晶状体外胚层从立方体转变为假复层上皮。当视神经囊接近头外胚层时，此过程发生在前胎盘前外胚层中，并受转录因子Pax6和分泌的BMP4调节。由于细胞和ECM具有相互依赖和调节的动态关系，我们假设ECM在晶状体placode形成过程中随着细胞形状的变化而演变。这项研究调查了光学ECM的变化，包括蛋白质分布沉积，使用鸡和小鼠模型在早期视神经发育过程中的细胞外明胶酶活性和基因表达模式。特别是,金属蛋白酶抑制剂Timp2的表达，对应于视神经ECM内明胶酶活性的降低。此外，我们证明，视ECM重塑取决于placode中的BMP信号传导。一起,我们的研究结果表明,晶状体平台在眼发育早期的视ECM重塑中起着积极的作用.
