Wnt/β-catenin signaling influences the proliferation and differentiation of progenitor populations in the hippocampus and subventricular zone. It is not known whether β-catenin signaling occurs in other progenitors populations of the adult nervous system, nor whether β-catenin is involved in the activation these progenitor populations after injury. The research outlined in this dissertation aims to answer those two questions: (1) is β-catenin signaling a common pathway used by progenitor populations of the adult nervous system? (2) how does β-catenin signaling change following injury'?

After introducing β-catenin signaling and its role in stein cells biology in Chapter 1, I utilize a β-catenin reporter mouse in Chapter 2 and show that (3-catenin signaling is a common pathway used by adult neural progenitors. My analysis shows that β-catenin signaling occurs in NG2 chondroitin sulfate proteoglycan+ (NG2) progenitors, in subcallosal zone (SCZ) progenitors, and in subependymal cells surrounding the central canal.

Given that stem cell populations become activated after injury, Chapter 3 of this dissertation explores the response of β-catenin signaling following traumatic brain injury (TBI) and spinal cord injury (SCI). Cells with β-catenin signaling increase following TBI but not SCI. Initially, most β-catenin signaling occurs in NG2+ progenitors; however, at seven days post injury the majority of β-catenin signaling is in astrocytes. Bromodeoxyuridine (BrdU) paradigms and infusions with the mitotic inhibitor cytosine arabinoside (AraC) show that the increase in β-catenin signaling occurs in newly born cells. β-catenin signaling does not increase in subependymal progenitors, NG2+ progenitors, or astrocytes following SCI.

Chapter 4 outlines studies manipulating β-catenin signaling in vivo after TBI in an effort to elucidate the function of β-catenin signaling in posttraumatic gliogenesis. I utilize pharmacologic and genetic approaches to show that β-catenin signaling does not affect the proliferation or number of astrocytes after injury.

Finally, Chapter 5 summarizes the main findings of this dissertation and elaborates on the implications of this work. As a whole, this thesis illustrates that β-catenin signaling is a common pathway used in progenitor populations of the adult nervous system and suggests manipulating the Wnt/β-catenin pathway after TBI as a way to modify posttraumatic gliogenesis.