Notch pathway molecules are essential for the maintenance, but not the generation, of mammalian neural stem cells
AUTOR(ES)
Hitoshi, Seiji
FONTE
Cold Spring Harbor Laboratory Press
RESUMO
Neural stem cells, which exhibit self-renewal and multipotentiality, are generated in early embryonic brains and maintained throughout the lifespan. The mechanisms of their generation and maintenance are largely unknown. Here, we show that neural stem cells are generated independent of RBP-Jκ, a key molecule in Notch signaling, by using RBP-Jκ−/− embryonic stem cells in an embryonic stem cell-derived neurosphere assay. However, Notch pathway molecules are essential for the maintenance of neural stem cells; they are depleted in the early embryonic brains of RBP-Jκ−/− or Notch1−/− mice. Neural stem cells also are depleted in embryonic brains deficient for the presenilin1 (PS1) gene, a key regulator in Notch signaling, and are reduced in PS1+/− adult brains. Both neuronal and glial differentiation in vitro were enhanced by attenuation of Notch signaling and suppressed by expressing an active form of Notch1. These data are consistent with a role for Notch signaling in the maintenance of the neural stem cell, and inconsistent with a role in a neuronal/glial fate switch.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=186324Documentos Relacionados
- Primitive neural stem cells from the mammalian epiblast differentiate to definitive neural stem cells under the control of Notch signaling
- Hsp90 Is Essential for the Synthesis and Subsequent Membrane Association, But Not the Maintenance, of the Src-Kinase p56lck
- The lipid phosphatase myotubularin is essential for skeletal muscle maintenance but not for myogenesis in mice
- Chromatin assembly factor I contributes to the maintenance, but not the re-establishment, of silencing at the yeast silent mating loci
- Sphingolipids are essential for differentiation but not growth in Leishmania