Abstract
Wnt/β-catenin signaling can influence the proliferation and differentiation of progenitor populations in the hippocampus and subventricular zone, known germinal centers in the adult mouse brain. It is not known whether β-catenin signaling occurs in quiescent glial progenitors in cortex or spinal cord, nor is it known whether β-catenin is involved in the activation of glial progenitor populations after injury. Using a β-catenin reporter mouse (BATGAL mouse), we show that β-catenin signaling occurs in NG2 chondroitin sulfate proteoglycan+ (NG2) progenitors in the cortex, in subcallosal zone (SCZ) progenitors, and in subependymal cells surrounding the central canal. Interestingly, cells with β-catenin signaling increased in the cortex and SCZ following traumatic brain injury (TBI) but did not following spinal cord injury. Initially after TBI, β-catenin signaling was predominantly increased in a subset of NG2+ progenitors in the cortex. One week following injury, the majority of β-catenin signaling appeared in reactive astrocytes but not oligodendrocytes. Bromodeoxyuridine (BrdU) paradigms and Ki-67 staining showed that the increase in β-catenin signaling occurred in newly born cells and was sustained after cell division. Dividing cells with β-catenin signaling were initially NG2+; however, by four days after a single injection of BrdU, they were predominantly astrocytes. Infusing animals with the mitotic inhibitor cytosine arabinoside prevented the increase of β-catenin signaling in the cortex, confirming that the majority of β-catenin signaling after TBI occurs in newly born cells. These data argue for manipulating the Wnt/β-catenin pathway after TBI as a way to modify post-traumatic gliogenesis.
Original language | English (US) |
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Pages (from-to) | 297-307 |
Number of pages | 11 |
Journal | STEM CELLS |
Volume | 28 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2010 |
Keywords
- Brain injury
- Gliosis
- Neural stem cell
- Spinal cord injury
- Wnt
ASJC Scopus subject areas
- Molecular Medicine
- Developmental Biology
- Cell Biology