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First published online January 27, 2005
doi: 10.1242/10.1242/dev.01619

Development 132, 751-762 (2005)
Published by The Company of Biologists 2005
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Arx homeobox gene is essential for development of mouse olfactory system

Sei-ichi Yoshihara1, Kayo Omichi2, Masako Yanazawa2, Kunio Kitamura2,*,{dagger} and Yoshihiro Yoshihara1,{dagger}

1 Laboratory for Neurobiology of Synapse, RIKEN Brain Science Institute, Wako-shi, Saitama 351-0198, Japan
2 Mitsubishi Kagaku Institute of Life Sciences, Machida-shi, Tokyo 194-8511, Japan

{dagger} Authors for correspondence (e-mail: yoshihara{at}brain.riken.go.jp or kitamura{at}ncnp.go.jp)

Accepted 15 December 2004

The olfactory system provides an excellent model in which to study cell proliferation, migration, differentiation, axon guidance, dendritic morphogenesis, and synapse formation. We report here crucial roles of the Arx homeobox gene in the developing olfactory system by analyzing its mutant phenotypes. Arx protein was expressed strongly in the interneurons and weakly in the radial glia of the olfactory bulb, but in neither the olfactory sensory neurons nor bulbar projection neurons. Arx-deficient mice showed severe anatomical abnormalities in the developing olfactory system: (1) size reduction of the olfactory bulb, (2) reduced proliferation and impaired entry into the olfactory bulb of interneuron progenitors, (3) loss of tyrosine hydroxylase-positive periglomerular cells, (4) disorganization of the layer structure of the olfactory bulb, and (5) abnormal axonal termination of olfactory sensory neurons in an unusual axon-tangled structure, the fibrocellular mass. Thus, Arx is required for not only the proper developmental processes of Arx-expressing interneurons, but also the establishment of functional olfactory neural circuitry by affecting Arx-non-expressing sensory neurons and projection neurons. These findings suggest a likely role of Arx in regulating the expression of putative instructive signals produced in the olfactory bulb for the proper innervation of olfactory sensory axons.

Key words: Arx, Olfactory bulb, Granule cells, Periglomerular cells, Rostral migratory stream, Radial glia, Olfactory axons, Axon guidance, Fibrocellular mass, Mouse




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