Jing Xiaotang, Malicki Jarema
Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
Development. 2009 Sep;136(17):2955-64. doi: 10.1242/dev.037739.
Although microtubule-dependent motors are known to play many essential functions in eukaryotic cells, their role in the context of the developing vertebrate embryo is less well understood. Here we show that the zebrafish ale oko (ako) locus encodes the p50 component of the dynactin complex. Loss of ako function results in a degeneration of photoreceptors and mechanosensory hair cells. Additionally, mutant Müller cells lose apical processes and their perikarya translocate rapidly towards the vitreal surface of the retina. This is accompanied by the accumulation of the apical determinants Nok and Has/aPKC in their cell bodies. ako is required cell-autonomously for the maintenance of the apical process but not for cell body positioning in Müller glia. At later stages, the retinotectal projection also degenerates in ako mutants. These results indicate that the p50 component of the dynactin complex is essential for the survival of sensory neurons and the maintenance of ganglion cell axons, and functions as a major determinant of apicobasal polarity in retinal radial glia.
尽管已知微管依赖型马达蛋白在真核细胞中发挥着许多重要功能,但其在脊椎动物胚胎发育过程中的作用却鲜为人知。在此,我们表明斑马鱼ale oko(ako)基因座编码动力蛋白复合体的p50组分。ako功能缺失导致光感受器和机械感觉毛细胞退化。此外,突变的穆勒细胞失去顶端突起,其胞体迅速向视网膜玻璃体表面移位。这伴随着顶端决定因子Nok和Has/aPKC在其细胞体内的积累。ako对于穆勒胶质细胞顶端突起的维持是细胞自主必需的,但对于细胞体定位并非必需。在后期,ako突变体中视网膜-脑顶盖投射也会退化。这些结果表明,动力蛋白复合体的p50组分对于感觉神经元的存活和神经节细胞轴突的维持至关重要,并且作为视网膜放射状胶质细胞顶-基极性的主要决定因素发挥作用。