Notch activity levels control the balance between quiescence and recruitment of adult neural stem cells.
The limited generation of neurons during adulthood is controlled by a balance between quiescence and recruitment of neural stem cells (NSCs). We use here the germinal zone of the zebrafish adult telencephalon to examine how the frequency of NSC divisions is regulated. We show, using several in vivo techniques, that progenitors transit back and forth between the quiescent and dividing state, according to varying levels of Notch activity: Notch induction drives progenitors into quiescence, whereas blocking Notch massively reinitiates NSC division and subsequent commitment toward becoming neurons. Notch activation appears predominantly triggered by newly recruited progenitors onto their neighbors, suggesting an involvement of Notch in a self-limiting mechanism, once neurogenesis is started. These results identify for the first time a lateral inhibition-like mechanism in the context of adult neurogenesis and suggest that the equilibrium between quiescence and neurogenesis in the adult brain is controlled by fluctuations of Notch activity, thereby regulating the amount of adult-born neurons.
Zebrafish Neurogenetics Department, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764 Neuherberg, Germany. chapouton@helmholtz-muenchen.de
Prisca
P
Chapouton
Paulina
P
Skupien
Birgit
B
Hesl
Marion
M
Coolen
John C
JC
Moore
Romain
R
Madelaine
Elizabeth
E
Kremmer
Theresa
T
Faus-Kessler
Patrick
P
Blader
Nathan D
ND
Lawson
Laure
L
Bally-Cuif
D053687:Adult Stem Cells / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism; D013687:Telencephalon / Q000166:cytology*; D015027:Zebrafish
D009414:Nerve Growth Factors; D018809:Proliferating Cell Nuclear Antigen; D051880:Receptors, Notch; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D049452:Green Fluorescent Proteins