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The Journal of Neuroscience, July 27, 2005, 25(30):6997-7003; doi:10.1523/JNEUROSCI.1435-05.2005

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Development/Plasticity/Repair
Pax6 Is Required for Making Specific Subpopulations of Granule and Periglomerular Neurons in the Olfactory Bulb

Minoree Kohwi,¹ Noriko Osumi,³ John L. R. Rubenstein,² and Arturo Alvarez-Buylla¹

¹Department of Neurological Surgery and Program in Developmental and Stem Cell Biology and ²Center for Neurobiology and Psychiatry, University of California, San Francisco, San Francisco, California 94143, and ³Division of Developmental Neuroscience, Center for Translational and Advanced Animal Research, Tohoku University School of Medicine, Sendai 980-8575, Japan

The subventricular zone (SVZ) produces different subclasses of olfactory bulb (OB) interneurons throughout life. Little is known about the molecular mechanisms controlling the production of different types of interneurons. Here we show that most proliferating adult SVZ progenitors express the transcription factor Pax6, but only a small subpopulation of migrating neuroblasts and new OB interneurons derived from these progenitors retains Pax6 expression. To elucidate the cell-autonomous role of Pax6 in OB neurogenesis, we transplanted green fluorescent protein-expressing embryonic forebrain progenitors of the dorsal lateral ganglionic eminence from Pax6 mutant Small Eye (Pax6^Sey/Sey) mice into the SVZ of adult wild-type mice. Pax6^Sey/Sey progenitors produce neuroblasts capable of migrating into the OB but fail to generate dopaminergic periglomerular and superficial granule cells. Interestingly, superficial granule neurons also express mRNA for tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis. Our data show that SVZ neuroblasts are heterogeneous and that Pax6 is required in a cell-autonomous manner for the production of cells in the dopaminergic lineage.

Key words: adult neurogenesis; olfactory bulb; dopaminergic periglomerular cells; interneurons; Sey; mouse

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Received April 12, 2005; revised June 7, 2005; accepted June 9, 2005.

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