Department of Biological Sciences, Walther Cancer Institute, Eck Institute for Global Health, University of Notre Dame, Notre Dame, Indiana 46556, USA.
Dev Neurobiol. 2010 Jun;70(7):473-84. doi: 10.1002/dneu.20788.
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-1a (Sema1a) 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 Sema1a signaling were found to induce cellular growth in these assays. Furthermore, immunohistochemical analyses indicated that NetA and Sema1a signaling induce expression of several growth regulators, including myc, cycD, cdk4, PCNA, and MapK in the wing disc. These data illustrate that NetA and Sema1a can specifically promote growth through induction of key cellular growth regulators. The abilities of NetA and Sema1a to regulate cellular growth are likely critical to their functions in both nervous system development and oncogenesis.
尽管轴突导向调节因子与轴突生长有关，但导向分子对细胞生长的影响还不太清楚。使用果蝇翅 imaginal 盘，一种上皮组织和一个用于分析细胞生长调节的特征良好的系统，允许在不存在轴突导向这一混杂因素的情况下，分析导向分子对细胞生长的影响。在本研究中，研究了 Netrin A（NetA）和 Semaphorin-1a（Sema1a）信号在翅膀发育过程中对细胞生长的影响。通过在发育中的翅盘中的体细胞克隆中调节这些基因的水平，评估了克隆区域以及克隆细胞的个体大小。在这些实验中发现 NetA 和 Sema1a 信号会诱导细胞生长。此外，免疫组织化学分析表明，NetA 和 Sema1a 信号在 wing disc 中诱导了几种生长调节剂的表达，包括 myc、cycD、cdk4、PCNA 和 MapK。这些数据表明，NetA 和 Sema1a 可以通过诱导关键的细胞生长调节剂来特异性地促进生长。NetA 和 Sema1a 调节细胞生长的能力可能对它们在神经系统发育和肿瘤发生中的功能至关重要。
