Institute of Structural and Molecular Biology, University College London, London, WC1E 6BT, UK.
Mech Dev. 2010 Jul-Aug;127(7-8):321-8. doi: 10.1016/j.mod.2010.04.004. Epub 2010 Apr 24.
Lens regeneration in adult salamanders occurs at the pupillary margin of the mid-dorsal iris where pigmented epithelial cells (PEC) re-enter the cell cycle and transdifferentiate into lens. It is not understood how the injury caused by removal of the lens (lentectomy) in one location is linked to initiating the response in a different spatial location (dorsal iris) and to this particular sector. We propose that the blood provides a link between the localised coagulation and signal transduction pathways that lead to regeneration. A transmembrane protein (tissue factor) is expressed in a striking patch-like domain in the dorsal iris of the newt that localises coagulation specifically to this location, but is not expressed in the axolotl, a related species that does not show thrombin activation after lentectomy and cannot regenerate its lens. Our hypothesis is that tissue factor expression localises the initiation of regeneration through the activation of thrombin and the recruitment of blood cells, leading to local growth factor release. This is the first example of gene expression in a patch of cells that prefigures the location of a regenerative response, and links the immune system with the initiation of a regenerative program.
成体蝾螈的晶状体再生发生在中背虹膜的瞳孔边缘,那里的色素上皮细胞 (PEC) 重新进入细胞周期并转分化为晶状体。目前尚不清楚在一个位置(晶状体切除术)引起的损伤如何与在不同的空间位置(背虹膜)和特定扇区启动反应相关联。我们提出,血液提供了连接局部凝血和信号转导途径的桥梁,这些途径导致了再生。一种跨膜蛋白(组织因子)在蝾螈的背虹膜中以明显的斑片状域表达,该蛋白将凝血特异性地定位到该位置,但在axolotl 中不表达,axolotl 是一种相关物种,在晶状体切除术后不会激活凝血酶,也不能再生其晶状体。我们的假设是,组织因子的表达通过激活凝血酶和募集血细胞来定位再生的起始,从而导致局部生长因子的释放。这是细胞斑片表达基因的第一个例子,预示着再生反应的位置,并将免疫系统与再生程序的启动联系起来。