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细胞黏附及肌动蛋白动力学因子促进移植果蝇感光细胞的轴突延伸和突触形成。

Cell adhesion and actin dynamics factors promote axonal extension and synapse formation in transplanted Drosophila photoreceptor cells.

机构信息

School of Life Science and Technology, Tokyo Institute of Technology, Yokahama, Japan.

Research Initiatives and Promotion Organization, Yokohama National University, Yokohama, Japan.

出版信息

Dev Growth Differ. 2024 Apr;66(3):205-218. doi: 10.1111/dgd.12916. Epub 2024 Feb 25.

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

视觉是通过从光感受器细胞延伸的轴突将光刺激传输到大脑而形成的。这些轴突的损伤会导致视力丧失。尽管通过移植研究了神经回路的再生,但实现精确的轴突投射仍然具有挑战性。为了通过移植实现视神经再生,我们利用了果蝇的视觉系统。我们之前建立了一种利用从眼盘中提取的光感受器前体细胞对果蝇进行移植的方法。然而,观察到移植细胞向大脑中的 lamina 延伸的轴突很少。我们通过修改移植细胞的选择过程来验证向 lamina 的轴突延伸。此外,我们专注于 N-钙粘蛋白(Ncad),一种细胞粘附因子,以及 Twinstar(Tsr),它已被证明可促进损伤神经中的肌动蛋白重组并诱导轴突伸长。Ncad 和 tsr 的过表达促进了轴突向 lamina 的延伸,以及延伸轴突中突触前结构的形成。此外,发现编码一种已被确定为突触组织者的蛋白质的 Neurexin-1(Nrx-1)的过表达不仅促进了突触前形成,而且还促进了轴突伸长。通过引入 Ncad、tsr 和 Nrx-1,我们不仅成功地实现了移植细胞向大脑中超出视网膜的轴突投射,而且还证实了移植细胞向更深的神经节——medulla 的投射。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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5416/11457513/f0673d3f4744/DGD-66-205-g002.jpg

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