p107 regulates neural precursor cells in the mammalian brain.
Here we show a novel function for Retinoblastoma family member, p107 in controlling stem cell expansion in the mammalian brain. Adult p107-null mice had elevated numbers of proliferating progenitor cells in their lateral ventricles. In vitro neurosphere assays revealed striking increases in the number of neurosphere forming cells from p107(-/-) brains that exhibited enhanced capacity for self-renewal. An expanded stem cell population in p107-deficient mice was shown in vivo by (a) increased numbers of slowly cycling cells in the lateral ventricles; and (b) accelerated rates of neural precursor repopulation after progenitor ablation. Notch1 was up-regulated in p107(-/-) neurospheres in vitro and brains in vivo. Chromatin immunoprecipitation and p107 overexpression suggest that p107 may modulate the Notch1 pathway. These results demonstrate a novel function for p107 that is distinct from Rb, which is to negatively regulate the number of neural stem cells in the developing and adult brain.
Vanderluit
Jacqueline L
JL
Neuroscience Research Group, Ottawa Health Research Institute, Ottawa, Ontario, Canada.
Ferguson
Kerry L
KL
Nikoletopoulou
Vassiliki
V
Parker
Maura
M
Ruzhynsky
Vladimir
V
Alexson
Tania
T
McNamara
Stephen M
SM
Park
David S
DS
Rudnicki
Michael
M
Slack
Ruth S
RS
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001921:Brain / Q000166:cytology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D051880:Receptors, Notch; D016160:Retinoblastoma Protein / Q000235:genetics*; D013234:Stem Cells / Q000378:metabolism*
D008565:Membrane Proteins; D012333:RNA, Messenger; D051880:Receptors, Notch; D016160:Retinoblastoma Protein; D001973:Bromodeoxyuridine