Bhlhb5::flpo allele uncovers a requirement for Bhlhb5 for the development of the dorsal cochlear nucleus.
Bhlhb5::flpo allele uncovers a requirement for Bhlhb5 for the development of the dorsal cochlear nucleus.
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DOI：
10.1016/j.ydbio.2016.04.028
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发表时间：
2016-06-15
影响因子：
2.7
通讯作者：
Ross SE
中科院分区：
文献类型：
--
作者：
Cai X;Kardon AP;Snyder LM;Kuzirian MS;Minestro S;de Souza L;Rubio ME;Maricich SM;Ross SE
听觉信息在传递到大脑之前首先在耳蜗核中进行处理。耳蜗核被细分为背侧、前腹侧和后腹侧区域，每个区域都包含几个亚型的神经元，这些神经元被认为在声音处理中发挥离散的作用。然而，这些神经元的个体发育知之甚少，这种知识上的差距阻碍了理解这个核的基本神经回路的努力。在这里，我们发现，Bhlhb5的兴奋性（单极刷细胞）和抑制性神经元（侧手翻细胞）的DCN在发展过程中表达。为了获得DCN中表达Bhlhb5的神经元的遗传途径，我们产生了Bhlhb5：：flpo敲入等位基因。使用交叉遗传策略，我们标记了侧手翻细胞，从而提供了概念证明，表达Bhlhb5的神经元的亚群可以被遗传靶向。此外，使用该等位基因的命运作图实验显示，Bhlhb5是DCN正常发育所必需的，因为缺乏Bhlhb5的小鼠显示出神经元数量的急剧减少，包括单极刷状细胞和侧手翻细胞。有趣的是，Bhlhb5：：flpo等位基因还在遗传上标记了神经系统中处理感觉输入的许多其他区域，包括背角、视网膜和外侧嗅束核，暗示Bhlhb5在介导感觉整合的神经元发育中具有更普遍的作用。
Auditory information is initially processed in the cochlear nuclei before being relayed to the brain. The cochlear nuclei are subdivided into dorsal, anterior ventral, and posterior ventral domains, each containing several subtypes of neurons that are thought to play discrete roles in the processing of sound. However, the ontogeny of these neurons is poorly understood, and this gap in knowledge hampers efforts to understand the basic neural circuitry of this nucleus. Here, we reveal that Bhlhb5 is expressed in both excitatory (unipolar brush cells) and inhibitory neurons (cartwheel cells) of the DCN during development. To gain genetic access to Bhlhb5-expressing neurons in the DCN, we generated a Bhlhb5::flpo knockin allele. Using an intersectional genetic strategy, we labeled cartwheel cells, thereby providing proof of concept that subpopulations of Bhlhb5-expressing neurons can be genetically targeted. Moreover, fate-mapping experiments using this allele revealed that Bhlhb5 is required for the proper development of the DCN, since mice lacking Bhlhb5 showed a dramatically diminished number of neurons, including unipolar brush and cartwheel cells. Intriguingly, the Bhlhb5::flpo allele also genetically labels numerous other regions of the nervous system that process sensory input, including the dorsal horn, the retina, and the nucleus of the lateral olfactory tract, hinting at a more general role for Bhlhb5 in the development of neurons that mediate sensory integration.