Nonautonomous Regulation of Neuronal Migration by Insulin Signaling, DAF-16/FOXO, and PAK-1
| Autor: | Steven C.D.L. Pham, Alla Grishok, Lisa M. Kennedy |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Neurogenesis
Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine PAK1 Mediator Cell Movement Animals Insulin Caenorhabditis elegans Caenorhabditis elegans Proteins p21-activated kinases Transcription factor lcsh:QH301-705.5 030304 developmental biology Neurons 0303 health sciences biology Kinase fungi Forkhead Transcription Factors Cell biology Insulin receptor p21-Activated Kinases lcsh:Biology (General) biology.protein Signal transduction 030217 neurology & neurosurgery Signal Transduction Transcription Factors |
| Zdroj: | Cell Reports, Vol 4, Iss 5, Pp 996-1009 (2013) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2013.07.045 |
| Popis: | SummaryNeuronal migration is essential for nervous system development in all organisms and is regulated in the nematode, C. elegans, by signaling pathways that are conserved in humans. Here, we demonstrate that the insulin/IGF-1-PI3K signaling pathway modulates the activity of the DAF-16/FOXO transcription factor to regulate the anterior migrations of the hermaphrodite-specific neurons (HSNs) during embryogenesis of C. elegans. When signaling is reduced, DAF-16 is activated and promotes migration; conversely, when signaling is enhanced, DAF-16 is inactivated, and migration is inhibited. We show that DAF-16 acts nonautonomously in the hypodermis to promote HSN migration. Furthermore, we identify PAK-1, a p21-activated kinase, as a downstream mediator of insulin/IGF-1-DAF-16 signaling in the nonautonomous control of HSN migration. Because a FOXO-Pak1 pathway was recently shown to regulate mammalian neuronal polarity, our findings indicate that the roles of FOXO and Pak1 in neuronal migration are most likely conserved from C. elegans to higher organisms. |
| Databáze: | OpenAIRE |
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