MBR-1, a novel helix-turn-helix transcription factor, is required for pruning excessive neurites in Caenorhabditis elegans

MBR-1, a novel helix-turn-helix transcription factor, is required for pruning excessive neurites in Caenorhabditis elegans
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DOI:
10.1016/j.cub.2005.07.057
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发表时间:
2005-09-06
期刊:
影响因子:
9.2
通讯作者:
Kubo, T
Kubo, T
中科院分区:
生物学1区
文献类型:
--
作者:
Kage, E;Hayashi, Y;Kubo, T

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在发育中的大脑中,过多的神经突在神经回路的构建和重塑中被积极修剪。我们首次证明,修剪的神经突发生在简单的神经回路秀丽隐杆线虫和一种新的转录因子,MBR-1,参与了这一过程。我们将MBR-1鉴定为C。Mblk-1是一种转录因子,优先在蜜蜂大脑的蘑菇体中表达[1]。虽然Mblk-1同源物在动物物种中是保守的,但它们在神经系统中的作用从未被分析过。我们使用C。elegans是研究神经元发育的理想模型动物。MBR-1在头和尾神经节的各种神经元中表达。mbr-1表达的神经元的形态学的比较显示,连接左右AIM中间神经元的过多的神经突在野生型中的幼虫阶段被消除,但在mbr-1突变体中持续到成虫阶段。此外,mbr-1的表达是由POU结构域转录因子nc-86调节的,并且在unc-86突变体中过度AIM连接的修剪受损。这些发现为神经突修剪的进一步遗传解剖提供了重要线索。
In the developing brain, excessive neurites are actively pruned in the construction and remodeling of neural circuits. We demonstrate for the first time that the pruning of neurites occurs in the simple neural circuit of Caenorhabditis elegans and that a novel transcription factor, MBR-1, is involved in this process. We identified MBR-1 as a C. elegans ortholog of Mblk-1, a transcription factor that is expressed preferentially in the mushroom bodies of the honeybee brain [1]. Although Mblk-1 homologs are conserved among animal species, their roles in the nervous system have never been analyzed. We used C. elegans as an ideal model animal for analysis of neuronal development. mbr-1 is expressed in various neurons in the head and tail ganglia. A comparison of the morphology of mbr-1-expressing neurons revealed that excessive neurites connecting the left and right AIM interneurons are eliminated during larval stages in wild-type but are sustained through the adult stage in the mbr-1 mutant. In addition, mbr-1 expression is regulated by UNC-86, a POU domain transcription factor, and the pruning of the excessive AIM connection is impaired in the unc-86 mutant. These findings provide an important clue for further genetic dissection of neurite pruning.