c-Myb is required for neural progenitor cell proliferation and maintenance of the neural stem cell niche in adult brain.
Ongoing production of neurons in adult brain is restricted to specialized neurogenic niches. Deregulated expression of genes controlling homeostasis of neural progenitor cell division and/or their microenvironment underpins a spectrum of brain pathologies. Using conditional gene deletion, we show that the proto-oncogene c-myb regulates neural progenitor cell proliferation and maintains ependymal cell integrity in mice. These two cellular compartments constitute the neurogenic niche in the adult brain. Brains devoid of c-Myb showed enlarged ventricular spaces, ependymal cell abnormalities, and reduced neurogenesis. Neural progenitor cells lacking c-Myb showed a reduced intrinsic proliferative capacity and reduction of Sox-2 and Pax-6 expression. These data point to an important role for c-Myb in the neurogenic niche of the adult brain.
Malaterre
Jordane
J
Differentiation and Transcription Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
Mantamadiotis
Theo
T
Dworkin
Sebastian
S
Lightowler
Sally
S
Yang
Qing
Q
Ransome
Mark I
MI
Turnley
Ann M
AM
Nichols
Nancy R
NR
Emambokus
Nikla R
NR
Frampton
Jon
J
Ramsay
Robert G
RG
D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005136:Eye Proteins / Q000096:biosynthesis; D015870:Gene Expression; D005786:Gene Expression Regulation; D020570:Genes, myb; D018398:Homeodomain Proteins / Q000096:biosynthesis; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors; D015534:Trans-Activators / Q000096:biosynthesis
D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012333:RNA, Messenger; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D015534:Trans-Activators