Microglia instruct subventricular zone neurogenesis.
Microglia are increasingly implicated as a source of non-neural regulation of postnatal neurogenesis and neuronal development. To evaluate better the contributions of microglia to neural stem cells (NSCs) of the subventricular neuraxis, we employed an adherent culture system that models the continuing proliferation and differentiation of the dissociated neuropoietic subventricular tissues. In this model, neuropoietic cells retain the ability to self-renew and form multipotent neurospheres, but progressively lose the ability to generate committed neuroblasts with continued culture. Neurogenesis in highly expanded NSCs can be rescued by coculture with microglial cells or microglia-conditioned medium, indicating that microglia provide secreted factor(s) essential for neurogenesis, but not NSC maintenance, self-renewal, or propagation. Our findings suggest an instructive role for microglial cells in contributing to postnatal neurogenesis in the largest neurogenic niche of the mammalian brain.
Walton
Noah M
NM
Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA.
Sutter
Benjamin M
BM
Laywell
Eric D
ED
Levkoff
Lindsay H
LH
Kearns
Sean M
SM
Marshall
Gregory P
GP
Scheffler
Bjorn
B
Steindler
Dennis A
DA
D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D020547:Lateral Ventricles / Q000166:cytology / Q000254:growth & development; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018874:Spheroids, Cellular / Q000166:cytology / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D013687:Telencephalon / Q000166:cytology / Q000254:growth & development*
D017077:Culture Media, Conditioned; D036341:Intercellular Signaling Peptides and Proteins