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Developmental regulation of linkers of the nucleoskeleton to the cytoskeleton during mouse postnatal retinogenesis

机译：小鼠出生后视网膜发生过程中核骨架与细胞骨架连接子的发育调控

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Sun proteins and nesprins are two families of proteins whose direct interactions across the nuclear envelope provide for the core of linkers of the nucleoskeleton to the cytoskeleton (LINC complexes) that physically connect the nucleus interior to cytoskeletal networks. Whereas LINC complexes play essential roles in nuclear migration anchorage and underlie normal CNS development, the developmental regulation of their composition remains largely unknown. In this study, we examined the spatiotemporal expression of lamins, Sun proteins and nesprins during postnatal mouse retinal development. Whereas retinal precursor cells mostly express B-type lamins, Sun1, and high molecular weight isoforms of nesprins, post-mitotic retinal cells are characterized by a drastic downregulation of the latter, the expression of A-type lamins, and the strong induction of a specific isoform of nesprin1 late in retinal development. Importantly, our results emphasize different spatiotemporal expression for nesprin1 and nesprin2 and further suggest an important role for KASH-less isoforms of nesprin1 in the CNS. In conclusion, the transition from retinal precursor cells undergoing interkinetic nuclear migration to post-mitotic retinal cells undergoing nuclear translocation and/or anchorage is accompanied by a profound remodeling of LINC complexes composition. This remodeling may reflect different requirements of nuclear dynamics at different stages of CNS development.
机译：Sun蛋白质和nesprins是两个蛋白质家族，其跨核被膜的直接相互作用提供了核骨架与细胞骨架（LINC复合体）的连接子的核心，后者物理上将细胞核内部连接到细胞骨架网络。尽管LINC复合物在核迁移锚固中起着重要作用，并且是中枢神经系统正常发育的基础，但其组成的发育调控仍然未知。在这项研究中，我们检查了产后小鼠视网膜发育过程中lamins，Sun蛋白和nesprins的时空表达。视网膜前体细胞主要表达B型lamins，Sun1和内斯普林的高分子量同工型，而有丝分裂后的视网膜细胞的特征是后者的急剧下调，A型lamin的表达以及强力诱导视网膜发育后期nesprin1的特定同工型。重要的是，我们的结果强调了nesprin1和nesprin2的时空表达不同，并且进一步表明了nesprin1在CNS中无KASH异构体的重要作用。总之，从经历过核运动间迁移的视网膜前体细胞到经历核易位和/或锚定的有丝分裂后视网膜细胞的过渡伴随着LINC复合物组成的深刻重塑。这种重塑可能反映了中枢神经系统发展不同阶段对核动力学的不同要求。

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