Regulated temporal-spatial astrocyte precursor cell proliferation involves BRAF signalling in mammalian spinal cord
An-Chi Tien1, Hui-Hsin Tsai, Anna V Molofsky
1Department of Pediatrics, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research and Howard Hughes Medical Institute, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
Mammalian astrocyte precursor proliferation involves two distinct cell types, radial glia (RG) and intermediate astrocyte precursors (IAP). BRAF signaling controls this proliferation during spinal cord development.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Astrocyte population expansion is key in complex organisms.
- Regulation of mammalian astrocyte precursor proliferation is not well understood.
Purpose of the Study:
- Identify and characterize distinct astrocyte precursor cell types.
- Investigate the regulation of astrocyte precursor proliferation during mammalian spinal cord development.
Main Methods:
- Utilized Aldh1L1-GFP to identify and distinguish astrocyte precursors.
- Employed conditional BRAF gene manipulation (loss and activation) in vivo.
- Assessed proliferation patterns and ERK signaling activity.
Main Results:
- Identified radial glia (RG) and intermediate astrocyte precursors (IAP) as distinct proliferative cell types.
- Discovered a ventral-to-dorsal proliferation pattern correlated with ERK signaling.
- Demonstrated BRAF signaling regulates astrocyte production, with BRAFV600E causing hyperproliferation, partially restricted by p16INK4A-p19(ARF).
Conclusions:
- Astrocyte precursor proliferation involves distinct RG and IAP cells.
- Proliferation is spatiotemporally controlled during spinal cord development.
- BRAF signaling is crucial for early mammalian astrocyte precursor proliferation.
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