Inhibitory and excitatory subtypes of cochlear nucleus neurons are defined by distinct bHLH transcription factors, Ptf1a and Atoh1.
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.
Fujiyama
Tomoyuki
T
Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Kodaira, Tokyo 187-8502, Japan.
Yamada
Mayumi
M
Terao
Mami
M
Terashima
Toshio
T
Hioki
Hiroyuki
H
Inoue
Yukiko U
YU
Inoue
Takayoshi
T
Masuyama
Norihisa
N
Obata
Kunihiko
K
Yanagawa
Yuchio
Y
Kawaguchi
Yoshiya
Y
Nabeshima
Yo-Ichi
Y
Hoshino
Mikio
M
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology; D017626:Cochlear Nucleus / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D004848:Epithelium / Q000502:physiology; D051379:Mice; D009154:Mutation; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D051792:Basic Helix-Loop-Helix Proteins; D014157:Transcription Factors; C500943:Atoh1 protein, mouse; C062602:transcription factor PTF1