A conserved PTEN/FOXO pathway regulates neuronal morphology during C. elegans development

Ryan Christensen, L. de la Torre-Ubieta, Azad Bonni, Daniel A. Colón-Ramos

Research output: Contribution to journalArticle

36 Scopus citations

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.

Original languageEnglish
Pages (from-to)5257-5267
Number of pages11
JournalDevelopment
Volume138
Issue number23
DOIs
StatePublished - Dec 1 2011

Keywords

  • Axon outgrowth
  • Dendrite morphology
  • FOXO
  • Neurodevelopment
  • PTEN

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    Christensen, R., de la Torre-Ubieta, L., Bonni, A., & Colón-Ramos, D. A. (2011). A conserved PTEN/FOXO pathway regulates neuronal morphology during C. elegans development. Development, 138(23), 5257-5267. https://doi.org/10.1242/dev.069062