Beta-catenin signaling increases in proliferating NG2+ progenitors and astrocytes during post-traumatic gliogenesis in the adult brain.
Wnt/beta-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 beta-catenin signaling occurs in quiescent glial progenitors in cortex or spinal cord, nor is it known whether beta-catenin is involved in the activation of glial progenitor populations after injury. Using a beta-catenin reporter mouse (BATGAL mouse), we show that beta-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 beta-catenin signaling increased in the cortex and SCZ following traumatic brain injury (TBI) but did not following spinal cord injury. Initially after TBI, beta-catenin signaling was predominantly increased in a subset of NG2+ progenitors in the cortex. One week following injury, the majority of beta-catenin signaling appeared in reactive astrocytes but not oligodendrocytes. Bromodeoxyuridine (BrdU) paradigms and Ki-67 staining showed that the increase in beta-catenin signaling occurred in newly born cells and was sustained after cell division. Dividing cells with beta-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 beta-catenin signaling in the cortex, confirming that the majority of beta-catenin signaling after TBI occurs in newly born cells. These data argue for manipulating the Wnt/beta-catenin pathway after TBI as a way to modify post-traumatic gliogenesis.
White
Bryan D
BD
Program in Neurobiology and Behavior, University of Washington School of Medicine and Institute for Stem Cell and Regenerative Medicine, Seattle, WA 98109, USA.
Nathe
Ryan J
RJ
Maris
Don O
DO
Nguyen
Nghi K
NK
Goodson
Jamie M
JM
Moon
Randall T
RT
Horner
Philip J
PJ
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism / Q000503:physiopathology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D005260:Female; D005904:Glial Fibrillary Acidic Protein; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000503:physiopathology; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
D011508:Chondroitin Sulfate Proteoglycans; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D051176:beta Catenin; C528900:glial fibrillary astrocytic protein, mouse