Beta-catenin signaling occurs in progenitors of the adult nervous system and increases in NG2+ progenitors and astrocytes during posttraumatic gliogenesis.

摘要

Wnt/beta-catenin signaling influences the proliferation and differentiation of progenitor populations in the hippocampus and subventricular zone. It is not known whether beta-catenin signaling occurs in other progenitors populations of the adult nervous system, nor whether beta-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 beta-catenin signaling a common pathway used by progenitor populations of the adult nervous system? (2) how does beta-catenin signaling change following injury'?;After introducing beta-catenin signaling and its role in stein cells biology in Chapter 1, I utilize a beta-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 beta-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 beta-catenin signaling following traumatic brain injury (TBI) and spinal cord injury (SCI). Cells with beta-catenin signaling increase following TBI but not SCI. Initially, most beta-catenin signaling occurs in NG2+ progenitors; however, at seven days post injury the majority of beta-catenin signaling is in astrocytes. Bromodeoxyuridine (BrdU) paradigms and infusions with the mitotic inhibitor cytosine arabinoside (AraC) show that the increase in beta-catenin signaling occurs in newly born cells. beta-catenin signaling does not increase in subependymal progenitors, NG2+ progenitors, or astrocytes following SCI.;Chapter 4 outlines studies manipulating beta-catenin signaling in vivo after TBI in an effort to elucidate the function of beta-catenin signaling in posttraumatic gliogenesis. I utilize pharmacologic and genetic approaches to show that beta-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 beta-catenin signaling is a common pathway used in progenitor populations of the adult nervous system and suggests manipulating the Wnt/beta-catenin pathway after TBI as a way to modify posttraumatic gliogenesis.