Institute of Developmental Biology and Molecular Medicine, School of Life Science, Fudan University, Shanghai 200433, China.
Hum Mol Genet. 2011 Mar 15;20(6):1061-73. doi: 10.1093/hmg/ddq549. Epub 2010 Dec 21.
Nuclear movement relative to cell bodies is a fundamental process during certain aspects of mammalian retinal development. During the generation of photoreceptor cells in the cell division cycle, the nuclei of progenitors oscillate between the apical and basal surfaces of the neuroblastic layer (NBL). This process is termed interkinetic nuclear migration (INM). Furthermore, newly formed photoreceptor cells migrate and form the outer nuclear layer (ONL). In the current study, we demonstrated that a KASH domain-containing protein, Syne-2/Nesprin-2, as well as SUN domain-containing proteins, SUN1 and SUN2, play critical roles during INM and photoreceptor cell migration in the mouse retina. A deletion mutation of Syne-2/Nesprin-2 or double mutations of Sun1 and Sun2 caused severe reduction of the thickness of the ONL, mislocalization of photoreceptor nuclei and profound electrophysiological dysfunction of the retina characterized by a reduction of a- and b-wave amplitudes. We also provide evidence that Syne-2/Nesprin-2 forms complexes with either SUN1 or SUN2 at the nuclear envelope to connect the nucleus with dynein/dynactin and kinesin molecular motors during the nuclear migrations in the retina. These key retinal developmental signaling results will advance our understanding of the mechanism of nuclear migration in the mammalian retina.
核相对于细胞体的运动是哺乳动物视网膜发育某些方面的基本过程。在细胞分裂周期中光感受器细胞的产生过程中，前体细胞的核在神经上皮层（NBL）的顶端和基底表面之间振荡。这个过程被称为核周运动（INM）。此外，新形成的光感受器细胞迁移并形成外核层（ONL）。在本研究中，我们证明了包含 KASH 结构域的蛋白 Syne-2/Nesprin-2 以及包含 SUN 结构域的蛋白 SUN1 和 SUN2 在 INM 和光感受器细胞迁移过程中在小鼠视网膜中发挥关键作用。Syne-2/Nesprin-2 的缺失突变或 SUN1 和 SUN2 的双突变导致 ONL 厚度严重减少，光感受器核的位置错误以及视网膜的电生理学功能严重障碍，表现为 a-和 b-波幅度降低。我们还提供了证据表明，Syne-2/Nesprin-2 在核周与 SUN1 或 SUN2 形成复合物，在核周运动期间将核与动力蛋白/dynactin 和驱动蛋白分子马达连接起来。这些关键的视网膜发育信号结果将促进我们对哺乳动物视网膜核迁移机制的理解。
