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Distinct roles for prominin-1 and photoreceptor cadherin in outer segment disc morphogenesis in CRISPR-altered X. laevis
Journal of Cell Science ( IF 4 ) Pub Date : 2021-01-11 , DOI: 10.1242/jcs.253906
Brittany J Carr 1 , Paloma Stanar 2 , Orson L Moritz 2
Affiliation  

Brittany J. Carr, Paloma Stanar, and Orson L. Moritz

Mutations in prominin-1 (prom1) and photoreceptor cadherin (cdhr1) are associated with inherited retinal degenerative disorders but their functions remain unknown. Here, we used CRISPR-Cas9 to generate prom1-null, cdhr1-null, and prom1 plus cdhr1 double-null Xenopus laevis and then documented the effects of these mutations on photoreceptor structure and function. Prom1-null mutations resulted in severely dysmorphic photoreceptors comprising overgrown and disorganized disc membranes. Cone outer segments were more severely affected than rods and had an impaired electroretinogram response. Cdhr1-null photoreceptors did not appear grossly dysmorphic, but ultrastructural analysis revealed that some disc membranes were overgrown or oriented vertically within the plasma membrane. Double-null mutants did not differ significantly from prom1-null mutants. Our results indicate that neither prom1 nor cdhr1 are necessary for outer segment disc membrane evagination or the fusion event that controls disc sealing. Rather, they are necessary for the higher-order organization of the outer segment. Prom1 may align and reinforce interactions between nascent disc leading edges, a function more critical in cones for structural support. Cdhr1 may secure discs in a horizontal orientation prior to fusion and regulate cone lamellae size.

This article has an associated First Person interview with the first author of the paper.



中文翻译:

Prominin-1 和光感受器钙粘蛋白在 CRISPR 改变的 X. laevis 外节盘形态发生中的不同作用

布列塔尼·J·卡尔、帕洛玛·斯塔纳尔和奥森·L·莫里茨

prominin-1 ( prom1 ) 和光感受器钙粘蛋白 ( cdhr1 ) 的突变与遗传性视网膜退行性疾病相关,但它们的功能仍不清楚。在这里,我们使用 CRISPR-Cas9 生成prom1 -null、cdhr1 -null 和prom1 加 cdhr1双无效非洲 爪蟾,然后记录这些突变对光感受器结构和功能的影响。Prom1缺失突变导致光感受器严重变形,包括过度生长和紊乱的椎间盘膜。视锥细胞外节比视杆细胞受到更严重的影响,并且视网膜电图反应受损。Cdhr1缺失的光感受器并未表现出严重的畸形,但超微结构分析显示,一些椎间盘膜过度生长或在质膜内垂直定向。双无效突变体与prom1无效突变体没有显着差异。我们的结果表明,prom1cdhr1都不是外节椎间盘膜外翻或控制椎间盘密封的融合事件所必需的。相反,它们对于外部部分的高阶组织是必要的。Prom1 可以对齐并增强新生椎间盘前缘之间的相互作用,这对于锥体的结构支撑来说更为重要。Cdhr1 可以在融合之前将椎间盘固定在水平方向并调节锥体薄片尺寸。

本文有对该论文第一作者的相关第一人称采访。

更新日期:2021-01-14
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