Induction of Cellular Growth by the Axon Guidance Regulators Netrin A and Semaphorin-1a

Induction of Cellular Growth by the Axon Guidance Regulators Netrin A and Semaphorin-1a
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DOI:
10.1002/dneu.20788
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发表时间:
2010-06-01
影响因子:
3
通讯作者:
Duman-Scheel, Molly
Duman-Scheel, Molly
中科院分区:
医学3区
文献类型:
--
作者:
Flannery, Ellen;VanZomeren-Dohm, Adrienne;Duman-Scheel, Molly

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虽然神经突生长与轴突导向调节因子有关,但导向分子对细胞生长的影响还不清楚。使用果蝇翅成虫盘,上皮组织和良好的表征系统的细胞生长调节的分析,允许在轴突指导不是混杂因素的设置中分析指导分子对细胞生长的影响。在这项调查中,Netrin A(NetA)和Semaphorin-la(Semala)信号传导对细胞生长的影响在翅膀发育过程中进行了检查。这些基因的水平调制在发育中的翅盘体细胞克隆,克隆面积,以及克隆细胞的个体大小进行了评估。发现NetA和Semala信号传导在这些测定中诱导细胞生长。此外,免疫组织化学分析表明,NetA和Semala信号诱导几种生长调节因子的表达,包括myc,cycD,cdk 4,PCNA和MapK在翼盘。这些数据表明,NetA和Semala可以通过诱导关键的细胞生长调节因子来特异性地促进生长。NetA和Semala调节细胞生长的能力可能对其在神经系统发育和肿瘤发生中的功能至关重要。(C)2010 Wiley Periodicals,Inc.开发神经生物学70:473- 484,2010
Although neurite outgrowth has been linked to axon guidance regulators, the effects of guidance molecules on cellular growth are not well understood. Use of the Drosophila wing imaginal disc, an epithelial tissue and a well-characterized system for analysis of cellular growth regulation, permits analysis of the impacts of guidance molecules on cellular growth in a setting in which axon guidance is not a confounding factor. In this investigation, the impacts of Netrin A (NetA) and Semaphorin-la (Semala) signaling on cellular growth are examined during wing development. Levels of these genes were modulated in somatic clones in the developing wing disc, and clone areas, as well as individual sizes of clonal cells were assessed. NetA and Semala signaling were found to induce cellular growth in these assays. Furthermore, immunohistochemical analyses indicated that NetA and Semala signaling induce expression of several growth regulators, including myc, cycD, cdk4, PCNA, and MapK in the wing disc. These data illustrate that NetA and Semala can specifically promote growth through induction of key cellular growth regulators. The abilities of NetA and Semala to regulate cellular growth are likely critical to their functions in both nervous system development and oncogenesis. (C) 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 473-484,2010