Jagged1 signals in the postnatal subventricular zone are required for neural stem cell self-renewal.
Neural stem cells (NSCs) in the postnatal mammalian brain self-renew and are a source of neurons and glia. To date, little is known about the molecular and cellular mechanisms regulating the maintenance and differentiation of these multipotent progenitors. We show that Jagged1 is required by mitotic cells in the subventricular zone (SVZ) and stimulates self-renewal of multipotent epidermal growth factor-dependent NSCs. Jagged1-expressing cells line the adult SVZ and are juxtaposed to Notch1-expressing cells, some of which are putative NSCs. In vitro, endogenous Jagged1 acts through Notch1 to promote NSC maintenance and multipotency. In vivo, reducing Jagged1/Notch1 signaling decreases the number of proliferating cells in the SVZ. In addition, soluble Jagged1 promotes self-renewal and neurogenic potential of multipotent neural progenitors in vitro. Our findings suggest a central role for Jagged1 in the NSC niche in the SVZ for maintaining a population of NSCs in the postnatal brain.
Nyfeler
Yves
Y
Department of Molecular Embryology, Max-Planck Institute of Immunobiology, Freiburg, Germany.
Kirch
Robert D
RD
Mantei
Ned
N
Leone
Dino P
DP
Radtke
Freddy
F
Suter
Ueli
U
Taylor
Verdon
V
D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D020547:Lateral Ventricles / Q000166:cytology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000502:physiology*
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D000072099:Serrate-Jagged Proteins; D004815:Epidermal Growth Factor