1. BMP4 signaling in NPCs upregulates Bcl-xL to promote their survival in the presence of FGF-2
- Author
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Yasuki Ishizaki, Masae Naruse, Hanako Yamamoto, Masashi Kurachi, and Koji Shibasaki
- Subjects
0301 basic medicine ,animal structures ,Cell Survival ,bcl-X Protein ,Biophysics ,Apoptosis ,Bcl-xL ,Bone Morphogenetic Protein 4 ,Fibroblast growth factor ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Neural Stem Cells ,Precursor cell ,medicine ,Animals ,Progenitor cell ,Fibroblast ,Molecular Biology ,Cells, Cultured ,Cell Proliferation ,biology ,Microarray analysis techniques ,Chemistry ,Cell Differentiation ,Cell Biology ,Up-Regulation ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,embryonic structures ,biology.protein ,Fibroblast Growth Factor 2 ,Signal transduction ,030217 neurology & neurosurgery ,Signal Transduction ,Astrocyte - Abstract
We previously reported that BMP4 does not promote proliferation or differentiation of CD44-positive astrocyte precursor cells (APCs) but greatly promotes their survival in the presence of fibroblast growth factor-2 (FGF-2). In this study, we examined if BMP4 acts as a survival factor also for neural stem/progenitor cells (NPCs) isolated from ganglionic eminence of neonatal mouse brain. We found BMP4 promotes survival but not proliferation or differentiation of these cells, just as in the case for CD44-positive APCs. Microarray analysis revealed some candidate molecules in the signaling pathway downstream of BMP4. Among them, we focused on Id1 (inhibitor of DNA-binding 1) and Bcl-xL in this study. Expression of both genes was promoted in the presence of BMP4, and this promotion was reduced by dorsomorphin, an inhibitor of BMP4 signaling. Furthermore, cytochrome c release from mitochondria was significantly reduced in the presence of BMP4, suggesting up-regulation of Bcl-xL activity by BMP4. Id1 siRNA reduced the expression of Bcl-xL, and negated survival promoting effect of BMP4. These data suggest that BMP4 promotes survival of NPCs by enhancing the anti-apoptotic function of Bcl-xL via BMP4-Smad1/5/8-Id1 signaling.
- Published
- 2018