The Journal of Neuroscience, June 18, 2008, 28(25):6439-6452; doi:10.1523/JNEUROSCI.0700-08.2008
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Development/Plasticity/Repair
A Dlx2- and Pax6-Dependent Transcriptional Code for Periglomerular Neuron Specification in the Adult Olfactory Bulb
Monika S. Brill,1,2,3
Marina Snapyan,4
Hilde Wohlfrom,1,2,3
Jovica Ninkovic,2,3
Melanie Jawerka,1,2,3
Grant S. Mastick,5
Ruth Ashery-Padan,6
Armen Saghatelyan,4
Benedikt Berninger,1,2,3 and
Magdalena Götz1,2,3
1Department of Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, D-80336 Munich, Germany, 2Institute for Stem Cell Research, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764 Neuherberg, Germany, 3Munich Center for Integrated Protein Science, 81377 Munich, Germany, 4Unité de Neurobiologie Cellulaire, Centre de Recherche Université Laval Robert-Giffard, Québec, Québec, Canada G1J 2G3, 5Biology Department, University of Nevada, Reno, Reno, Nevada 89557, and 6Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv 69978, Tel Aviv, Israel
Correspondence should be addressed to Magdalena Götz at the above addresses. Email: magdalena.goetz{at}helmholtz-muenchen.de
Distinct olfactory bulb (OB) interneurons are thought to become specified depending on from which of the different subregions lining the lateral ventricle wall they originate, but the role of region-specific transcription factors (TFs) in the generation of OB interneurons diversity is still poorly understood. Despite the crucial roles of the Dlx family of TFs for patterning and neurogenesis in the ventral telencephalon during embryonic development, their role in adult neurogenesis has not yet been addressed. Here we show that in the adult brain, Dlx 1 and Dlx2 are expressed in progenitors of the lateral but not the dorsal subependymal zone (SEZ), thus exhibiting a striking regional specificity. Using retroviral vectors to examine the function of Dlx2 in a cell-autonomous manner, we demonstrate that this TF is necessary for neurogenesis of virtually all OB interneurons arising from the lateral SEZ. Beyond its function in generic neurogenesis, Dlx2 also plays a crucial role in neuronal subtype specification in the OB, promoting specification of adult-born periglomerular neurons (PGNs) toward a dopaminergic fate. Strikingly, Dlx2 requires interaction with Pax6, because Pax6 deletion blocks Dlx2-mediated PGN specification. Thus, Dlx2 wields a dual function by first instructing generic neurogenesis from adult precursors and subsequently specifying PGN subtypes in conjunction with Pax6.
Key words: neurogenesis; subependymal zone; olfactory bulb; transcription factor; tyrosine hydroxylase; stem cell
Received Feb. 15, 2008;
revised April 17, 2008;
accepted May 7, 2008.
Correspondence should be addressed to Magdalena Götz at the above addresses. Email: magdalena.goetz{at}helmholtz-muenchen.de