MAB-5/Hox regulates the Q neuroblast transcriptome, including cwn-1/Wnt, to mediate posterior migration in Caenorhabditis elegans.

IF 3.3 3区生物学

Genetics Pub Date : 2024-04-23 DOI:10.1093/genetics/iyae045

Vitoria K. Paolillo, Matthew E. Ochs, E. Lundquist

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引用次数: 0

Abstract

Neurogenesis involves the precisely coordinated action of genetic programs controlling large-scale neuronal fate specification down to terminal events of neuronal differentiation. The Q neuroblasts in Caenorhabditis elegans, QL on the left and QR on the right, divide, differentiate, and migrate in a similar pattern to produce three neurons each. However, QL on the left migrates posteriorly, and QR on the right migrates anteriorly. The MAB-5/Hox transcription factor is necessary and sufficient for posterior Q lineage migration and is normally expressed only in the QL lineage. To define genes controlled by MAB-5 in the Q cells, fluorescence-activated cell sorting was utilized to isolate populations of Q cells at a time in early L1 larvae when MAB-5 first becomes active. Sorted Q cells from wild-type, mab-5 loss-of-function (lof), and mab-5 gain-of-function (gof) mutants were subject to RNA-seq and differential expression analysis. Genes enriched in Q cells included those involved in cell division, DNA replication, and DNA repair, consist with the neuroblast stem cell identity of the Q cells at this stage. Genes affected by mab-5 included those involved in neurogenesis, neural development, and interaction with the extracellular matrix. cwn-1, which encodes a Wnt signaling molecule, showed a paired response to mab-5 in the Q cells: cwn-1 expression was reduced in mab-5(lof) and increased in mab-5(gof), suggesting that MAB-5 is required for cwn-1 expression in Q cells. MAB-5 is required to prevent anterior migration of the Q lineage while it transcriptionally reprograms the Q lineage for posterior migration. Functional genetic analysis revealed that CWN-1 is required downstream of MAB-5 to inhibit anterior migration of the QL lineage, likely in parallel to EGL-20/Wnt in a noncanonical Wnt pathway. In sum, work here describes a Q cell transcriptome, and a set of genes regulated by MAB-5 in the QL lineage. One of these genes, cwn-1, acts downstream of mab-5 in QL migration, indicating that this gene set includes other genes utilized by MAB-5 to facilitate posterior neuroblast migration.

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MAB-5/Hox调节Q神经母细胞转录组，包括cwn-1/Wnt，以介导秀丽隐杆线虫的后向迁移。

神经发生涉及基因程序的精确协调作用，这些程序控制着大范围神经元命运的规范，直至神经元分化的终端事件。秀丽隐杆线虫的 Q 神经母细胞（左侧为 QL，右侧为 QR）以相似的模式分裂、分化和迁移，各自产生三个神经元。不过，左侧的 QL 向后迁移，而右侧的 QR 则向前方迁移。MAB-5/Hox 转录因子是 Q 系向后迁移的必要和充分条件，通常只在 QL 系中表达。为了确定 Q 细胞中受 MAB-5 控制的基因，我们利用荧光激活细胞分选技术，在 L1 幼虫早期 MAB-5 开始活跃时分离 Q 细胞群。对野生型、mab-5 功能缺失（lof）和 mab-5 功能增益（gof）突变体的 Q 细胞进行了 RNA 序列和差异表达分析。Q细胞中富集的基因包括参与细胞分裂、DNA复制和DNA修复的基因，这与此阶段Q细胞的神经母细胞干细胞特征一致。编码Wnt信号分子的cwn-1在Q细胞中显示出与mab-5成对的反应：cwn-1在mab-5（lof）中表达减少，而在mab-5（gof）中表达增加，这表明MAB-5对Q细胞中cwn-1的表达是必需的。MAB-5是防止Q系向前方迁移所必需的，同时它还能转录重编程Q系向后方迁移。功能基因分析表明，CWN-1需要在MAB-5的下游抑制QL系的前向迁移，很可能与EGL-20/Wnt并行于非经典的Wnt通路。总之，本文描述了 Q 细胞转录组和 QL 系中受 MAB-5 调控的一组基因。其中一个基因cwn-1在QL迁移过程中作用于mab-5的下游，这表明该基因组包括MAB-5用于促进后部神经母细胞迁移的其他基因。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Genetics 生物-遗传学

CiteScore

6.20

自引率

6.10%

发文量

177

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