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

小鼠出生后视网膜形成过程中核骨架与细胞骨架连接体的发育调控

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作者:David S Razafsky, Candace L Ward, Thorsten Kolb, Didier Hodzic

Abstract

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.

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