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

Development. 2011 Dec;138(23):5257-67. doi: 10.1242/dev.069062.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Forkhead Transcription Factors
  • Immunohistochemistry
  • Microscopy, Fluorescence
  • Neurites / physiology*
  • Neurogenesis / physiology*
  • Phosphatidylinositol 3-Kinase / metabolism*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Signal Transduction / physiology*
  • Transcription Factors / metabolism*
  • Transgenes / genetics

Substances

  • Caenorhabditis elegans Proteins
  • DAF-18 protein, C elegans
  • Forkhead Transcription Factors
  • Protein Isoforms
  • RNA, Small Interfering
  • Transcription Factors
  • daf-16 protein, C elegans
  • Phosphatidylinositol 3-Kinase