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

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