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双皮质素相关基因 zyg-8 是秀丽隐杆线虫神经元中的微管组织者。

The doublecortin-related gene zyg-8 is a microtubule organizer in Caenorhabditis elegans neurons.

机构信息

CRBM-CNRS, Université Montpellier 2, 1919, route de Mende, 34293 Montpellier, France.

出版信息

J Cell Sci. 2012 Nov 15;125(Pt 22):5417-27. doi: 10.1242/jcs.108381. Epub 2012 Sep 6.

Abstract

Doublecortin-domain containing (DCDC) genes play key roles in the normal and pathological development of the human brain cortex. The origin of the cellular specialisation and the functional redundancy of these microtubule (MT)-associated proteins (MAPs), especially those of Doublecortin (DCX) and Doublecortin-like kinase (DCLKs) genes, is still unclear. The DCX domain has the ability to control MT architecture and bundling. However, the physiological significance of such properties is not fully understood. To address these issues, we sought post-mitotic roles for zyg-8, the sole representative of the DCX-DCLK subfamily of genes in C. elegans. Previously, zyg-8 has been shown to control anaphase-spindle positioning in one-cell stage embryos, but functions of the gene later in development have not been investigated. Here we show that wild-type zyg-8 is required beyond early embryonic divisions for proper development, spontaneous locomotion and touch sensitivity of adult worms. Consistently, we find zyg-8 expression in the six touch receptor neurons (TRNs), as well as in a subset of other neuronal and non-neuronal cells. In TRNs and motoneurons, zyg-8 controls cell body shape/polarity and process outgrowth and morphology. Ultrastructural analysis of mutant animals reveals that zyg-8 promotes structural integrity, length and number of individual MTs, as well as their bundled organisation in TRNs, with no impact on MT architecture.

摘要

双皮质素结构域(DCDC)基因在人类大脑皮层的正常和病理发育中起着关键作用。这些微管(MT)相关蛋白(MAPs),特别是双皮质素(DCX)和双皮质素样激酶(DCLKs)基因的细胞特化和功能冗余的起源仍然不清楚。DCX 结构域具有控制 MT 结构和束状的能力。然而,这种特性的生理意义尚不完全清楚。为了解决这些问题,我们在秀丽隐杆线虫中寻找了唯一代表 DCX-DCLK 亚家族的 zyg-8 的有丝分裂后作用。以前,zyg-8 被证明可以控制单细胞期胚胎的后期纺锤体定位,但该基因在发育后期的功能尚未被研究。在这里,我们表明野生型 zyg-8 在早期胚胎分裂后对正常发育、成年线虫的自发运动和触觉敏感性是必需的。一致地,我们发现 zyg-8 在六个触觉感受器神经元(TRNs)以及其他一些神经元和非神经元细胞中表达。在 TRNs 和运动神经元中,zyg-8 控制细胞体形状/极性以及突起的生长和形态。对突变动物的超微结构分析表明,zyg-8 促进了 TRNs 中单个 MT 的结构完整性、长度和数量,以及它们的束状组织,对 MT 结构没有影响。

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