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The Journal of Neuroscience, November 1, 2006, 26(44):11359-11370; doi:10.1523/JNEUROSCI.2247-06.2006

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Development/Plasticity/Repair
The Transcriptional Coactivator Querkopf Controls Adult Neurogenesis

Tobias D. Merson, Mathew P. Dixon, Caitlin Collin, Rodney L. Rietze, Perry F. Bartlett, Tim Thomas, ^* and Anne K. Voss ^*

The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia

Correspondence should be addressed to either of the following at the above address: Anne K. Voss, Email: avoss{at}wehi.edu.au; or Tim Thomas, E-mail: Email: tthomas{at}wehi.edu.au

The adult mammalian brain maintains populations of neural stem cells within discrete proliferative zones. Understanding of the molecular mechanisms regulating adult neural stem cell function is limited. Here, we show that MYST family histone acetyltransferase Querkopf (Qkf, Myst4, Morf)-deficient mice have cumulative defects in adult neurogenesis in vivo, resulting in declining numbers of olfactory bulb interneurons, a population of neurons produced in large numbers during adulthood. Qkf-deficient mice have fewer neural stem cells and fewer migrating neuroblasts in the rostral migratory stream. Qkf gene expression is strong in the neurogenic subventricular zone. A population enriched in multipotent cells can be isolated from this region on the basis of Qkf gene expression. Neural stem cells/progenitor cells isolated from Qkf mutant mice exhibited a reduced self-renewal capacity and a reduced ability to produce differentiated neurons. Together, our data show that Qkf is essential for normal adult neurogenesis.

Key words: Qkf; transcription; chromatin; neural stem cells; adult neurogenesis; neuroblasts

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Received Oct. 27, 2005; revised Aug. 23, 2006; accepted Sept. 16, 2006.

Correspondence should be addressed to either of the following at the above address: Anne K. Voss, Email: avoss{at}wehi.edu.au; or Tim Thomas, E-mail: Email: tthomas{at}wehi.edu.au

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