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Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
Astrocytes negatively regulate neurogenesis through the Jagged1-mediated Notch pathway
Ulrika Wilhelmsson1, Maryam Faiz, Yolanda de Pablo
1Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Stem Cells (Dayton, Ohio)
|August 14, 2012
Summary
Astrocytes normally inhibit neurogenesis via Notch signaling. Removing glial fibrillary acidic protein (GFAP) and vimentin from astrocytes reduces Notch signaling, increasing neural stem cell differentiation and neurogenesis.
Area of Science:
- Neuroscience
- Cell Biology
- Stem Cell Biology
Background:
- Adult neurogenesis is crucial for brain function and plasticity.
- Astrocytes regulate the neurogenic niche through secreted and membrane-associated factors.
- The precise mechanisms by which astrocytes control neurogenesis are not fully understood.
Purpose of the Study:
- To elucidate the mechanisms by which astrocytes regulate neuronal differentiation and adult neurogenesis.
- To investigate the role of glial fibrillary acidic protein (GFAP) and vimentin in astrocyte-mediated regulation of neurogenesis.
- To determine the involvement of the Notch signaling pathway in astrocyte-dependent control of neural progenitor cells.
Main Methods:
- Primary astrocyte and neurosphere cocultures were utilized to assess neuronal differentiation.
- Studies involved astrocytes lacking glial fibrillary acidic protein (GFAP) and vimentin (GFAP(-/-) Vim(-/-)).
- Notch ligand Jagged1 endocytosis and signaling were analyzed, along with hippocampal neurogenesis in GFAP(-/-) Vim(-/-) mice.
Main Results:
- Astrocytes inhibit neuronal differentiation through cell-cell contact.
- GFAP(-/-) Vim(-/-) astrocytes exhibited reduced Jagged1 endocytosis and Notch signaling, leading to increased neuronal differentiation.
- The absence of GFAP and vimentin resulted in enhanced hippocampal neurogenesis in mice, both basally and after injury.
Conclusions:
- Astrocytes negatively regulate adult neurogenesis via the Notch pathway.
- Endocytosis of Jagged1 by astrocytes and subsequent Notch signaling to neural stem/progenitor cells are dependent on GFAP and vimentin.
- GFAP and vimentin are critical regulators of astrocyte-mediated neurogenesis.
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