RRC ID 46050
Author Christensen R, de la Torre-Ubieta L, Bonni A, Colón-Ramos DA.
Title A conserved PTEN/FOXO pathway regulates neuronal morphology during C. elegans development.
Journal 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.
Volume 138(23)
Pages 5257-67
Published 2011-12-1
DOI 10.1242/dev.069062
PII 138/23/5257
PMID 22069193
PMC PMC3210501
MeSH 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
IF 5.611
Times Cited 35
WOS Category DEVELOPMENTAL BIOLOGY
Resource
C.elegans tm399