調控神經發育之唐氏症細胞黏著蛋白細胞內區域具有調控細胞凋亡功能之研究

Abstract

In the retina, each type of neuron except photoreceptor rods and cones forms “Retinal mosaics” that covers the whole retina with an even spatial distribution. This pattern assures every horizontal cell, amacrine cell and retinal ganglion cell well-arranged within their layer, covering the entire retina without blind spot and dendrite overlapping. However, the mechanism behind the phenomenon remains unknown. Recent researchers find the apoptosis may take part in the formation of retina regularity. Mice with the pro-apoptotic gene bax knockout or overexpress of the antiapoptotic gene bcl-2 showed the disrupted spatial pattern. Intriguingly, the same phenotype has been reported in the dscam (Down’s syndrome cell adhesion molecules) knockout mice. Furthermore, in both condition, the dendrites of neighboring cell severely tangle together. Since the drosophila dscam gene participates in the cell-cell recognition using homophilic binding. Therefore, we hypothesize that Dscam may involve the retina apoptotic pathway through the homophilic interaction between the same cell types and lead to apoptosis-dependent retinal mosaic. Here we cloned the different versions of degenerative DSCAM expressing plasmid, including Full-length, Truncated, Extracellular and Intracellular DSCAM. To prove the DSCAM is crucial for the apoptosis, HEK cell was chosen for transfection. With the time-lapse recording and co-culture experiment, we successfully identified the N-terminal of DSCAM intracellular domain is crucial for triggering apoptosis via intrinsic pathway.