Abstract:
Vision is formed by the transmission of light stimuli to the brain through axons extending from photoreceptor cells. Damage to these axons leads to loss of vision. Despite research on neural circuit regeneration through transplantation, achieving precise axon projection remains challenging. To achieve optic nerve regeneration by transplantation, we employed the Drosophila visual system. We previously established a transplantation method for Drosophila utilizing photoreceptor precursor cells extracted from the eye disc. However, little axonal elongation of transplanted cells into the brain, the lamina, was observed. We verified axonal elongation to the lamina by modifying the selection process for transplanted cells. Moreover, we focused on N-cadherin (Ncad), a cell adhesion factor, and Twinstar (Tsr), which has been shown to promote actin reorganization and induce axon elongation in damaged nerves. Overexpression of Ncad and tsr promoted axon elongation to the lamina, along with presynaptic structure formation in the elongating axons. Furthermore, overexpression of Neurexin-1 (Nrx-1), encoding a protein identified as a synaptic organizer, was found to not only promote presynapse formation but also enhance axon elongation. By introducing Ncad, tsr, and Nrx-1, we not only successfully achieved axonal projection of transplanted cells to the brain beyond the retina, but also confirmed the projection of transplanted cells into a deeper ganglion, the medulla. The present study offers valuable insights to realize regeneration through transplantation in a more complex nervous system.
摘要:
视觉是通过从感光细胞延伸的轴突将光刺激传递到大脑而形成的。这些轴突的损伤导致视力丧失。尽管通过移植对神经回路再生进行了研究,实现精确的轴突投影仍然具有挑战性。通过移植实现视神经再生,我们使用了果蝇视觉系统。我们先前利用从眼盘中提取的感光前体细胞建立了果蝇的移植方法。然而,移植到大脑中的细胞轴突伸长很小,椎板,被观察到。我们通过修改移植细胞的选择过程来验证轴突向椎板的伸长。此外,我们专注于N-钙黏着蛋白(Ncad),细胞粘附因子,和Twinstar(Tsr),已被证明可促进肌动蛋白重组并诱导受损神经的轴突伸长。Ncad和tsr的过度表达促进轴突向叶片伸长,在伸长的轴突中形成突触前结构。此外,Neurexin-1(Nrx-1)过表达,编码一种被鉴定为突触组织者的蛋白质,发现不仅可以促进突触前的形成,而且可以增强轴突的伸长。通过介绍Ncad,tsr,和Nrx-1,我们不仅成功地实现了移植细胞到大脑的轴突投射,但也证实了移植细胞投射到更深的神经节中,髓质.本研究为在更复杂的神经系统中通过移植实现再生提供了有价值的见解。