Impaired retinal differentiation and maintenance in zebrafish laminin mutants
Impaired retinal differentiation and maintenance in zebrafish laminin mutants
复制标题
DOI：
10.1167/iovs.06-1212
复制
发表时间：
2007-06-01
影响因子：
4.4
通讯作者：
Neuhauss, Stephan C. F.
中科院分区：
文献类型：
--
作者：
Biehlmaier, Oliver;Makhankov, Yuri;Neuhauss, Stephan C. F.
目的。研究层粘连蛋白突变体Bashful(bal，LAMal)、暴躁(GUP，Lamb1)和嗜睡(Sly，LAMC1)3种斑马鱼视网膜的形态和生理变化。通过测试突变幼虫的视动反应(OKR)来观察它们的视觉行为缺陷。此外，还测量了视网膜电信号(ERG)，并通过标准组织学、免疫细胞化学、TUNEL法和电子显微镜观察了视网膜的形态。GUP和SLY在任何光照强度下都没有表现出OKR，而BAL胚胎在超过40%的对比度下表现出一些残留的OKR行为。与OKR结果一致的是，GUP和SLY在测试的任何光强下都没有表现出ERG反应，而Bal突变体在高光强下表现出较小的a波和b波。所有三个层粘连蛋白突变体都显示神经节细胞层改变、视神经束和晶状体缺陷。同样，BALL表现出最不严重的形态表型，没有额外的缺陷。相反，GUP和SLY均表现出严重的光感受器外段缩短和突触改变(浮动带)，细胞死亡增加。Lamb 1和lame1链在光感受器及其突触的形态发生中起着重要作用。相比之下，LAMal并不参与外层视网膜的发育。
Purpose. To characterize morphologic and physiological alterations in the retina of three laminin mutant zebrafish, bashful (bal, lamal), grumpy (gup, lamb1), and sleepy (sly, lamc1), which were identified in forward genetic screens and were found to be impaired in visual functions.Methods. Mutant larvae were observed for defects in visual behavior by testing their optokinetic response (OKR). In addition, electroretinograms (ERG) were measured and retinal morphology was examined by standard histology, immunocytochemistry, TUNEL assay, and electron microscopy.Results. Both, gup and sly showed no OKR at any light intensity tested, whereas bal embryos showed some remaining OKR behavior at more than 40% of contrast. Consistent with the OKR result, gup and sly did not show an ERG response at any light intensity tested, whereas bal mutants exhibited small a-and b-waves at high light intensities. All three laminin mutants showed altered ganglion cell layers, optic nerve fasciculations, and lens defects. Again, bal showed the least severe morphologic phenotype with no additional defects. In contrast, both, gup and sly, showed severe photoreceptor outer segment shortening and synapse alteration (floating ribbons) as well as increased cell death.Conclusions. Lamb 1 and lame1 chains play an important role in the morphogenesis of photoreceptors and their synapses. In contrast, lamal is not involved in outer retina development.