Notch pathway molecules are essential for the maintenance, but not the generation, of mammalian neural stem cells
Northwestern University · Ontario Institute for Cancer Research · +5 more institutions
Abstract
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-Jkappa, a key molecule in Notch signaling, by using RBP-Jkappa(-/-) 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-Jkappa(-/-) or Notch1(-/-) mice. Neural stem cells also are depleted in embryonic brains deficient for the presenilin1 (PS1) gene, a key…
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Authors
10- SHSeiji HitoshiCorresponding
Northwestern University, Ontario Institute for Cancer Research, Mount Sinai Hospital, University of Toronto, Lunenfeld-Tanenbaum Research Institute, Amgen (Canada), Case Western Reserve University
- TOTania O. Alexson
Northwestern University, Ontario Institute for Cancer Research, Mount Sinai Hospital, University of Toronto, Lunenfeld-Tanenbaum Research Institute, Amgen (Canada), Case Western Reserve University
- VTVincent Tropepe
Northwestern University, Ontario Institute for Cancer Research, Mount Sinai Hospital, University of Toronto, Lunenfeld-Tanenbaum Research Institute, Amgen (Canada), Case Western Reserve University
- DDDorit Donoviel
Northwestern University, Ontario Institute for Cancer Research, Mount Sinai Hospital, University of Toronto, Lunenfeld-Tanenbaum Research Institute, Amgen (Canada), Case Western Reserve University
- AEAndrew Elia
Northwestern University, Ontario Institute for Cancer Research, Mount Sinai Hospital, University of Toronto, Lunenfeld-Tanenbaum Research Institute, Amgen (Canada), Case Western Reserve University
Topics & keywords
- Neurosphere
- Notch signaling pathway
- Biology
- Neural stem cell
- Embryonic stem cell
- Cell biology
- Stem cell
- Hes3 signaling axis