c-Myb is Required for Neural Progenitor Cell Proliferation and Maintenance of the Neural Stem Cell Niche in Adult Brain

¹ Differentiation and Transcription Laboratory, Peter MacCallum Cancer Centre, East Melbourne, and Department of Pathology, University of Melbourne, Parkville, Vic, Australia
² Differentiation and Transcription Laboratory, Peter MacCallum Cancer Centre, East Melbourne, and Department of Pathology, University of Melbourne, Parkville, Vic, Australia; Department of Pharmaceutical Biology, Monash University, Parkville, Vic, Australia
³ Howard Florey Institute, Parkville, Vic, Australia
⁴ Centre for Neuroscience, University of Melbourne, Parkville, Vic, Australia
⁵ Department of Physiology, Monash University, Clayton, Vic, Australia
⁶ Institute for Biomedical Research, Birmingham University, Birmingham, United Kingdom

^* To whom correspondence should be addressed. E-mail: Theo.Mantamadiotis{at}vcp.monash.edu.au.

	Abstract

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.