title: Induction of cellular growth by the axon guidance regulators netrin A and semaphorin-1a.
abstract: 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.
authors.affiliation: Department of Biological Sciences, Walther Cancer Institute, Eck Institute for Global Health, University of Notre Dame, Notre Dame, Indiana 46556, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Flannery
authors.forename: Adrienne
authors.initials: A
authors.lastname: VanZomeren-Dohm
authors.forename: Paul
authors.initials: P
authors.lastname: Beach
authors.forename: Wendy Simanton
authors.initials: WS
authors.lastname: Holland
authors.forename: Molly
authors.initials: M
authors.lastname: Duman-Scheel
mesh_terms: D000818:Animals; D049108:Cell Enlargement; D002999:Clone Cells; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology / Q000254:growth & development*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D009414:Nerve Growth Factors / Q000235:genetics / Q000502:physiology*; D000075388:Netrin-1; D000075385:Netrins; D039961:Semaphorins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*; D014921:Wings, Animal / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors; C000617352:NetA protein, Drosophila; D000075385:Netrins; D039961:Semaphorins; D025521:Tumor Suppressor Proteins; C477531:semaphorin 1a, Drosophila; D000075388:Netrin-1