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剪接体成分中的突变以及……中突变体轴突导向缺陷的抑制因子的过表达

Mutations in the Spliceosome Component and Overexpression of Suppress Axon Guidance Defects of Mutants in .

作者信息

Aburegeba Zina, Pan Jie, Hutter Harald

机构信息

Department of Biological Sciences, Simon Fraser University, Burnaby, BC, Canada.

出版信息

Neurosci Insights. 2022 Sep 6;17:26331055221123346. doi: 10.1177/26331055221123346. eCollection 2022.

Abstract

During nervous system development, axons must navigate to specific target areas. In , the cadherin CDH-4 is required for ventral nerve cord axonal navigation, and dorsal nerve cord fasciculation. How CDH-4 mediates axon navigation and fasciculation is currently unknown. To identify genes acting together with , we isolated mutants suppressing the axon guidance defects of mutants. These suppressors showed partial suppression of axonal defects in the dorsal and ventral nerve cords seen in mutants. We identified one suppressor gene, , which encodes a component of the spliceosome. Complete loss-of-function alleles of are lethal, suggesting that the mutation isolated in our suppressor screen is a partial loss-of-function allele. A previous study found that RNAi-induced suppression of leads to changes in the expression of several 100 genes including the cadherin . We found that overexpression of mimics the suppression seen in mutants, suggesting that CDH-5 can partially compensate for the loss of CDH-4.

摘要

在神经系统发育过程中,轴突必须导航至特定的目标区域。在[具体情况未提及]中,钙黏蛋白CDH - 4是腹侧神经索轴突导航和背侧神经索成束所必需的。目前尚不清楚CDH - 4如何介导轴突导航和成束。为了鉴定与[未明确基因]共同作用的基因,我们分离出了抑制[未明确基因]突变体轴突导向缺陷的突变体。这些抑制子部分抑制了[未明确基因]突变体中背侧和腹侧神经索的轴突缺陷。我们鉴定出一个抑制基因[未明确基因],它编码剪接体的一个组分。[未明确基因]的完全功能丧失等位基因是致死的,这表明我们在抑制子筛选中分离出的突变是一个部分功能丧失等位基因。先前的一项研究发现,RNA干扰诱导的[未明确基因]抑制会导致包括钙黏蛋白[未明确基因]在内的数百个基因的表达发生变化。我们发现[未明确基因]的过表达模拟了[未明确基因]突变体中观察到的抑制现象,这表明CDH - 5可以部分补偿CDH - 4的缺失。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6368/9452795/8994486e0906/10.1177_26331055221123346-fig1.jpg

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