title: A conserved PTEN/FOXO pathway regulates neuronal morphology during C. elegans development.
abstract: The phosphatidylinositol 3-kinase (PI3K) signaling pathway is a conserved signal transduction cascade that is fundamental for the correct development of the nervous system. The major negative regulator of PI3K signaling is the lipid phosphatase DAF-18/PTEN, which can modulate PI3K pathway activity during neurodevelopment. Here, we identify a novel role for DAF-18 in promoting neurite outgrowth during development in Caenorhabditis elegans. We find that DAF-18 modulates the PI3K signaling pathway to activate DAF-16/FOXO and promote developmental neurite outgrowth. This activity of DAF-16 in promoting outgrowth is isoform-specific, being effected by the daf-16b isoform but not the daf-16a or daf-16d/f isoform. We also demonstrate that the capacity of DAF-16/FOXO in regulating neuron morphology is conserved in mammalian neurons. These data provide a novel mechanism by which the conserved PI3K signaling pathway regulates neuronal cell morphology during development through FOXO.
authors: Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Cell Biology, Yale University School of Medicine, P.O. Box 9812, New Haven, CT 06536-0812, USA.
authors: Ryan
authors: R
authors: Christensen
authors: Luis
authors: L
authors: de la Torre-Ubieta
authors: Azad
authors: A
authors: Bonni
authors: Daniel A
authors: DA
authors: Colón-Ramos
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D016501:Neurites / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; C116661:DAF-18 protein, C elegans; D051858:Forkhead Transcription Factors; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D058539:Phosphatidylinositol 3-Kinase