Notch1 and Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate

K Tanigaki; F Nogaki; J Takahashi; K Tashiro; H Kurooka; T Honjo

doi:10.1016/s0896-6273(01)00179-9

Notch1 and Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate

Neuron. 2001 Jan;29(1):45-55. doi: 10.1016/s0896-6273(01)00179-9.

Authors

K Tanigaki¹, F Nogaki, J Takahashi, K Tashiro, H Kurooka, T Honjo

Affiliation

¹ Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida-Konoe Sakyo, 606-8501, Kyoto, Japan.

PMID: 11182080
DOI: 10.1016/s0896-6273(01)00179-9

Abstract

Notch1 has been shown to induce glia in the peripheral nervous system. However, it has not been known whether Notch can direct commitment to glia from multipotent progenitors of the central nervous system. Here we present evidence that activated Notch1 and Notch3 promotes the differentiation of astroglia from the rat adult hippocampus-derived multipotent progenitors (AHPs). Quantitative clonal analysis indicates that the action of Notch is likely to be instructive. Transient activation of Notch can direct commitment of AHPs irreversibly to astroglia. Astroglial induction by Notch signaling was shown to be independent of STAT3, which is a key regulatory transcriptional factor when ciliary neurotrophic factor (CNTF) induces astroglia. These data suggest that Notch provides a CNTF-independent instructive signal of astroglia differentiation in CNS multipotent progenitor cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Astrocytes / metabolism*
Cell Differentiation / drug effects
Cell Lineage / drug effects
Cells, Cultured
Ciliary Neurotrophic Factor / metabolism
Ciliary Neurotrophic Factor / pharmacology
Clone Cells / drug effects
DNA-Binding Proteins / metabolism
Fibroblast Growth Factor 2 / metabolism*
Fibroblast Growth Factor 2 / pharmacology
Hippocampus / cytology
Hippocampus / metabolism
Membrane Proteins / metabolism*
Membrane Proteins / pharmacology
Neurons / cytology
Neurons / drug effects
Neurons / metabolism
Proto-Oncogene Proteins / metabolism*
Proto-Oncogene Proteins / pharmacology
Rats
Receptor, Notch1
Receptors, Cell Surface*
STAT3 Transcription Factor
Signal Transduction / drug effects
Stem Cells / cytology
Stem Cells / drug effects
Stem Cells / metabolism*
Trans-Activators / metabolism
Transcription Factors*

Substances

Ciliary Neurotrophic Factor
DNA-Binding Proteins
Membrane Proteins
Notch1 protein, rat
Proto-Oncogene Proteins
Receptor, Notch1
Receptors, Cell Surface
STAT3 Transcription Factor
Stat3 protein, rat
Trans-Activators
Transcription Factors
Fibroblast Growth Factor 2