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

Imagen de Daniel Alfonso Colón-Ramos
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TítuloA conserved PTEN/FOXO pathway regulates neuronal morphology during C. elegans development.
Publication TypeJournal Article
Year of Publication2011
AutoresChristensen, R, de la Torre-Ubieta, L, Bonni, A, Colón-Ramos, DA
JournalDevelopment
Volume138
Issue23
Pagination5257-67
Date Published2011 Dec
ISSN1477-9129
Palabras claveAnalysis of Variance, Animals, Animals, Genetically Modified, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Immunohistochemistry, Microscopy, Fluorescence, Neurites, Neurogenesis, Phosphatidylinositol 3-Kinase, Protein Isoforms, RNA Interference, RNA, Small Interfering, Signal Transduction, Transcription Factors, Transgenes
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.

DOI10.1242/dev.069062
Alternate JournalDevelopment
PubMed ID22069193