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The Journal of Neuroscience, January 15, 2003, 23(2):568-578

DLX5 Regulates Development of Peripheral and Central Components of the Olfactory System

Jason E. Long^{1, *}, Sonia Garel^{1, *}, Michael J. Depew^{1, *}, Stuart Tobet², and John L. R. Rubenstein¹

¹ Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, Programs in Biomedical Sciences, Developmental Biology, Neuroscience and Oral Biology, Langley Porter Psychiatric Institute, University of California, San Francisco, San Francisco, California 94143-0984, and ² The Shriver Center, Department of Biomedical Sciences and Physiology, University of Massachusetts Medical School, Waltham, Massachusetts 02452

Induction, neurogenesis, and synaptogenesis of the olfactory bulb are thought to require interactions with the olfactory epithelium. The Dlx family of homeobox genes is expressed in both the olfactory bulb and olfactory epithelium. In particular, Dlx5 is expressed in the olfactory placode, olfactory epithelium, and local circuit neurons of the olfactory bulb. Here we analyzed mice lacking DLX5 function. The Dlx5^/ mutation reduces the size of the olfactory epithelium. Although some olfactory neurons are formed, they fail to generate olfactory axons that innervate the olfactory bulb. Despite the lack of innervation, the olfactory bulb forms, and neurogenesis of projection and local circuit neurons proceeds. However, the mutation has a cell-autonomous effect on the ability of neural progenitors to produce olfactory bulb local circuit neurons, with granule cells more severely affected than periglomerular cells. In addition, the mutation has a noncell-autonomous effect on the morphogenesis of mitral cells.

Key words: Dlx5; local circuit neuron; olfactory bulb; olfactory epithelium; tangential migration; GABA

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^* J.E.L., S.G., and M.J.D. contributed equally to this work.

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Copyright © 2003 Society for Neuroscience  0270-6474/03/232568-11$05.00/0

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