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First published online 13 May 2009
doi: 10.1242/dev.033480

Development 136, 2049-2058 (2009)
Published by The Company of Biologists 2009
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Inhibitory and excitatory subtypes of cochlear nucleus neurons are defined by distinct bHLH transcription factors, Ptf1a and Atoh1

Tomoyuki Fujiyama1,2, Mayumi Yamada1,2, Mami Terao2, Toshio Terashima3, Hiroyuki Hioki4, Yukiko U. Inoue1, Takayoshi Inoue1, Norihisa Masuyama1, Kunihiko Obata5, Yuchio Yanagawa6, Yoshiya Kawaguchi7, Yo-ichi Nabeshima2 and Mikio Hoshino1,2,*

1 Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Kodaira, Tokyo 187-8502, Japan.
2 Department of Pathology and Tumor Biology, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
3 Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
4 Department of Morphological Brain Science and, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
5 Neuronal Circuit Mechanisms Research Group, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
6 Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
7 Department of Surgery, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.

* Author for correspondence (e-mail: hoshino{at}ncnp.go.jp)

Accepted 16 April 2009

The cochlear nucleus (CN), which consists of dorsal and ventral cochlear nuclei (DCN and VCN), plays pivotal roles in processing and relaying auditory information to the brain. Although it contains various types of neurons, the origins of the distinct subtypes and their developmental molecular machinery are still elusive. Here we reveal that two basic helix-loop-helix transcription factors play crucial roles in specifying neuron subtypes in the CN. Pancreatic transcription factor 1a (Ptf1a) and atonal homolog 1 (Atoh1) were found to be expressed in discrete dorsolateral regions of the embryonic neuroepithelia of the middle hindbrain (rhombomeres 2-5). Genetic lineage tracing using mice that express Cre recombinase from the Ptf1a locus or under the control of the Atoh1 promoter revealed that inhibitory (GABAergic and glycinergic) or excitatory (glutamatergic) neurons of both DCN and VCN are derived from the Ptf1a- and Atoh1-expressing neuroepithelial regions, respectively. In the Ptf1a or Atoh1 null embryos, production of inhibitory or excitatory neurons, respectively, was severely inhibited in the CN. These findings suggest that inhibitory and excitatory subtypes of CN neurons are defined by Ptf1a and Atoh1, respectively and, furthermore, provide important insights into understanding the machinery of neuron subtype specification in the dorsal hindbrain.

Key words: Hindbrain, Math1, bHLH transcription factor, Cochlear nucleus, Inhibitory, Excitatory, Mouse


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© The Company of Biologists Ltd 2009