Differential expression and subcellular localization of Copines in mouse retina
Differential expression and subcellular localization of Copines in mouse retina
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DOI：
10.1002/cne.24684
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发表时间：
2019-10-01
影响因子：
2.5
通讯作者：
Badea, Tudor C.
中科院分区：
文献类型：
--
作者：
Goel, Manvi;Li, Tiansen;Badea, Tudor C.
Brn 3转录因子的组合表达是视网膜神经节细胞（RGC）中细胞特异性形态发展所必需的。Brn 3s调节RGC类型特异性特征的分子机制在很大程度上未被探索。我们先前确定了Copine（Cpne）分子家族的几个成员作为视网膜中Brn 3转录因子的潜在靶点。我们现在使用原位杂交和免疫组织化学来表征Copine在出生后和成年小鼠视网膜中的表达。我们发现Cpne 5，6和9在无长突细胞和RGCs的神经节细胞层（GCL）和内核层（INL）中表达。Cpne 4表达仅限于INL的一个无长突细胞群，但特异性表达于GCL中的RGC。RGC中的Cpne 4表达受Brn 3b的调节，既有细胞自主调节（在Brn 3b（+）RGC中），也有细胞非自主调节（在Brn 3b（-）RGC中）。Copines在组织培养细胞（HEK 293）中过表达时表现出多种亚细胞分布，并且可以诱导在这些非神经元细胞中形成使人联想到神经突的细长突起。我们的研究结果表明，Copines可能参与Brn 3b依赖的RGC类型的规范中的组合方式。鉴于其表达谱和先前证明的作用，作为Ca 2+传感器，它们可能参与在出生后早期形成RGC树突和轴突形成的形态发生过程。
Combinatorial expression of Brn3 transcription factors is required for the development of cell-specific morphologies in retinal ganglion cells (RGCs). The molecular mechanisms by which Brn3s regulate RGC type specific features are largely unexplored. We previously identified several members of the Copine (Cpne) family of molecules as potential targets of Brn3 transcription factors in the retina. We now use in situ hybridization and immunohistochemistry to characterize Copine expression in the postnatal and adult mouse retina. We find that Cpne5, 6, and 9 are expressed in the ganglion cell layer (GCL) and inner nuclear layer (INL) in both amacrine cells and RGCs. Cpne4 expression is restricted to one amacrine cell population of the INL, but is specifically expressed in RGCs in the GCL. Cpne4 expression in RGCs is regulated by Brn3b both cell autonomously (in Brn3b(+) RGCs) and cell nonautonomously (in Brn3b(-) RGCs). Copines exhibit a variety of subcellular distributions when overexpressed in tissue culture cells (HEK293), and can induce the formation of elongated processes reminiscent of neurites in these non-neuronal cells. Our results suggest that Copines might be involved in a combinatorial fashion in Brn3b-dependent specification of RGC types. Given their expression profile and previously proven role as Ca2+ sensors, they may participate in the morphogenetic processes that shape RGC dendrite and axon formation at early postnatal ages.