Transplantation of photoreceptor precursor cells into the retina of an adult Drosophila

Transplantation of photoreceptor precursor cells into the retina of an adult Drosophila
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将感光前体细胞移植到成年果蝇的视网膜中

DOI:
10.1111/dgd.12545
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发表时间:
2018
期刊:
Development, Growth & Differentiation
影响因子:
--
通讯作者:
Suzuki Takashi
Suzuki Takashi
中科院分区:
--
文献类型:
--
作者:
Suzuki Takahisa;Oochi Keita;Hakeda-Suzuki Satoko;Suzuki Takashi

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通过视网膜前体神经元移植恢复感光细胞和大脑之间的连接,可以治愈由感光细胞和大脑之间的连接断开引起的失明。然而,即使在移植这些细胞后,仍然不清楚如何引导轴突从视网膜到大脑的长距离。为了建立一种引导移植神经元轴突的方法,我们使用了果蝇视觉系统。通过测试不同的条件,包括解离和预孵育时间,我们成功地建立了一种方法,将从三龄幼虫发育中的眼盘中分离的感光细胞前体细胞移植到成年视网膜中。此外,我们在移植物中过表达N-钙粘蛋白(CadN),因为已知它在发育阶段后的视叶中广泛表达,并持续到成年阶段。我们发现,使用CadN促进细胞粘附特性增强了移植的感光神经元的轴突长度,因此对于将来的移植是有用的。我们测试了CadN::Frazzled嵌合受体的过表达,发现轴突长度与我们的野生型移植物没有差异,表明CadN的细胞内结构域对于轴突伸长是必需的。总之,利用果蝇视觉系统,我们已经建立了一个很好的平台来探索移植神经元细胞轴突延伸所需的分子。从这个平台构建的未来研究将有助于基于移植的人类神经系统再生治疗。
Blindness caused by the disconnection between photoreceptor cells and the brain can be cured by restoring this connection through the transplantation of retinal precursor neurons. However, even after transplanting these cells, it is still unclear how to guide the axons over the long distance from the retina to the brain. To establish a method of guiding the axons of transplanted neurons, we used theDrosophilavisual system. By testing different conditions, including the dissociation and preincubation length, we have successfully established a method to transplant photoreceptor precursor cells isolated from the developing eye discs of third‐instar larvae into the adult retina. Moreover, we overexpressed N‐cadherin (CadN) in the transplant, since it is known to be broadly expressed in the optic lobe well after developmental stages, continuing through adult stages. We found that promoting the cell adhesive properties using CadN enhances the axonal length of the grafted photoreceptor neurons and therefore is useful for future transplantation. We tested the overexpression of a CadN::Frazzled chimeric receptor and found that there was no difference in axonal length from our wild‐type transplants, suggesting that the intracellular domain of CadN is necessary for axonal elongation. Altogether, using theDrosophilavisual system, we have established an excellent platform for exploring the molecules required for proper axon extension of transplanted neuronal cells. Future studies building from this platform will be useful for regenerative therapy of the human nervous system based on transplantation.
DOI: 10.1038/nn.2756
发表时间: 2011-03-01
影响因子: 25
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