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晶状体基板在眼睛早期发育过程中调节细胞外基质的形成。

Lens placode modulates extracellular matrix formation during early eye development.

机构信息

Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, 05508-900, Brazil.

Department of Ophthalmology and Visual Sciences and Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.

出版信息

Differentiation. 2024 Jul-Aug;138:100792. doi: 10.1016/j.diff.2024.100792. Epub 2024 Jun 22.

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)在形态发生的多个事件中的作用已被很好地描述,但对于其在早期眼睛发育中的具体作用知之甚少。晶状体发育中的第一个形态发生事件之一是基板增厚,这将假定的晶状体外胚层从立方体形变成假复层上皮。当视囊接近颅面外胚层时,这个过程发生在前基板外胚层中,并且受到转录因子 Pax6 和分泌的 BMP4 的调节。由于细胞和 ECM 之间存在相互依存和调节的动态关系,我们假设在晶状体基板形成过程中,细胞形状的变化会导致 ECM 发生演变。本研究使用鸡和鼠模型,研究了早期视发育过程中包括蛋白分布、沉积、细胞外明胶酶活性和基因表达模式在内的视 ECM 的变化。特别是,金属蛋白酶抑制剂 Timp2 的表达与视 ECM 中明胶酶活性的降低相对应。此外,我们证明了基板中的 BMP 信号对视神经 ECM 重塑的依赖性。综上所述,我们的研究结果表明,在早期眼睛发育过程中,晶状体基板在重塑视 ECM 中起着积极的作用。

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