-Catenin Signaling Increases in Proliferating NG2+ Progenitors and Astrocytes during Post-Traumatic Gliogenesis in the Adult Brain§||

摘要

Wnt/-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 -catenin signaling occurs in quiescent glial progenitors in cortex or spinal cord, nor is it known whether -catenin is involved in the activation of glial progenitor populations after injury. Using a -catenin reporter mouse (BATGAL mouse), we show that -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 -catenin signaling increased in the cortex and SCZ following traumatic brain injury (TBI) but did not following spinal cord injury. Initially after TBI, -catenin signaling was predominantly increased in a subset of NG2+ progenitors in the cortex. One week following injury, the majority of -catenin signaling appeared in reactive astrocytes but not oligodendrocytes. Bromodeoxyuridine (BrdU) paradigms and Ki-67 staining showed that the increase in -catenin signaling occurred in newly born cells and was sustained after cell division. Dividing cells with -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 -catenin signaling in the cortex, confirming that the majority of -catenin signaling after TBI occurs in newly born cells. These data argue for manipulating the Wnt/-catenin pathway after TBI as a way to modify post-traumatic gliogenesis. STEM CELLS 2010;28:297-307