Centre for Integrative Physiology, School of Biomedical Sciences, University of Edinburgh, Edinburgh, Scotland, UK.
BMC Neurosci. 2012 Feb 23;13:20. doi: 10.1186/1471-2202-13-20.
The mammalian thalamus relays sensory information from the periphery to the cerebral cortex for cognitive processing via the thalamocortical tract. The thalamocortical tract forms during embryonic development controlled by mechanisms that are not fully understood. β-catenin is a nuclear and cytosolic protein that transduces signals from secreted signaling molecules to regulate both cell motility via the cytoskeleton and gene expression in the nucleus. In this study we tested whether β-catenin is likely to play a role in thalamocortical connectivity by examining its expression and activity in developing thalamic neurons and their axons.
At embryonic day (E)15.5, the time when thalamocortical axonal projections are forming, we found that the thalamus is a site of particularly high β-catenin mRNA and protein expression. As well as being expressed at high levels in thalamic cell bodies, β-catenin protein is enriched in the axons and growth cones of thalamic axons and its growth cone concentration is sensitive to Netrin-1. Using mice carrying the β-catenin reporter BAT-gal we find high levels of reporter activity in the thalamus. Further, Netrin-1 induces BAT-gal reporter expression and upregulates levels of endogenous transcripts encoding β-actin and L1 proteins in cultured thalamic cells. We found that β-catenin mRNA is enriched in thalamic axons and its 3'UTR is phylogenetically conserved and is able to direct heterologous mRNAs along the thalamic axon, where they can be translated.
We provide evidence that β-catenin protein is likely to be an important player in thalamocortcial development. It is abundant both in the nucleus and in the growth cones of post-mitotic thalamic cells during the development of thalamocortical connectivity and β-catenin mRNA is targeted to thalamic axons and growth cones where it could potentially be translated. β-catenin is involved in transducing the Netrin-1 signal to thalamic cells suggesting a mechanism by which Netrin-1 guides thalamocortical development.
哺乳动物丘脑通过丘脑皮质束将来自外围的感觉信息中继到大脑皮层进行认知处理。丘脑皮质束在胚胎发育过程中形成，其机制尚未完全了解。β-连环蛋白是一种核蛋白和胞质蛋白，通过细胞骨架转导来自分泌信号分子的信号，从而调节细胞运动和核内基因表达。在这项研究中，我们通过检查其在发育中的丘脑神经元及其轴突中的表达和活性，来测试β-连环蛋白是否可能在丘脑皮质连接中发挥作用。
在胚胎发育第 15.5 天（E15.5），即丘脑皮质轴突投射形成时，我们发现丘脑是β-连环蛋白 mRNA 和蛋白表达特别高的部位。β-连环蛋白蛋白不仅在丘脑细胞体中高表达，而且在丘脑轴突的轴突和生长锥中富集，其生长锥浓度对 Netrin-1 敏感。使用携带β-连环蛋白报告基因 BAT-gal 的小鼠，我们发现丘脑中有高水平的报告基因活性。此外，Netrin-1 诱导 BAT-gal 报告基因表达，并上调培养的丘脑细胞中内源性β-actin 和 L1 蛋白编码转录本的水平。我们发现β-连环蛋白 mRNA 在丘脑轴突中富集，其 3'UTR 在系统发育上保守，并能指导异源 mRNA 沿丘脑轴突运输，在那里可以翻译。
我们提供的证据表明，β-连环蛋白蛋白可能是丘脑皮质发育的重要参与者。在丘脑皮质连接发育过程中，无论是在后生的丘脑细胞的核内还是在其有丝分裂后生长锥中，β-连环蛋白蛋白都很丰富。β-连环蛋白 mRNA 靶向丘脑轴突和生长锥，在那里它可能被翻译。β-连环蛋白参与转导 Netrin-1 信号到丘脑细胞，提示 Netrin-1 引导丘脑皮质发育的机制。
