Inhibitory and excitatory subtypes of cochlear nucleus neurons are defined by distinct bHLH transcription factors, Ptf1a and Atoh1
Inhibitory and excitatory subtypes of cochlear nucleus neurons are defined by distinct bHLH transcription factors, Ptf1a and Atoh1
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DOI：
10.1242/dev.033480
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发表时间：
2009-06-15
期刊：
影响因子：
4.6
通讯作者：
Hoshino, Mikio
中科院分区：
文献类型：
--
作者：
Fujiyama, Tomoyuki;Yamada, Mayumi;Hoshino, Mikio
耳蜗核（CN）由耳蜗背核（DCN）和耳蜗腹核（VCN）组成，在听觉信息的处理和传递中起着关键作用。虽然它包含各种类型的神经元，但不同亚型的起源及其发育分子机制仍然难以捉摸。在这里，我们揭示了两个基本的螺旋-环-螺旋转录因子在CN中指定神经元亚型中起着至关重要的作用。胰腺转录因子1a（Ptf 1a）和无调同源物1（Atoh 1）被发现表达在离散背外侧区域的胚胎神经上皮细胞的中后脑（菱形2-5）。使用表达来自Ptf 1a基因座或Atoh 1启动子控制下的Cre重组酶的小鼠进行遗传谱系追踪发现，DCN和VCN的抑制性（GABA能和甘氨酸能）或兴奋性（谷氨酸能）神经元分别来自Ptf 1a和Atoh 1表达的神经上皮区域。在Ptf 1a或Atoh 1空胚胎中，抑制性或兴奋性神经元的产生分别在CN中受到严重抑制。这些研究结果表明，抑制性和兴奋性亚型CN神经元的定义Ptf 1a和Atoh 1，分别，此外，提供重要的见解了解机械的神经元亚型规格在背侧后脑。
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.