Prdm13 Regulates Subtype Specification of Retinal Amacrine Interneurons and Modulates Visual Sensitivity
Prdm13 Regulates Subtype Specification of Retinal Amacrine Interneurons and Modulates Visual Sensitivity
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DOI：
10.1523/jneurosci.0089-15.2015
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发表时间：
2015-05-20
影响因子：
5.3
通讯作者：
Furukawa, Takahisa
中科院分区：
文献类型：
--
作者：
Watanabe, Satoshi;Sanuki, Rikako;Furukawa, Takahisa
无长突间神经元在视网膜的视觉信息处理中起着至关重要的作用，它在形态、神经化学和生理特征上具有高度的多样性。然而，对于每一种无长突细胞亚型在视觉上的指定机制和功能还不是很清楚。我们发现Prdm13转录调节因子在小鼠视网膜发育和成熟的无长突细胞中特异表达。大多数Prdm13阳性的无长突细胞是Calbindin和Calretinin阳性的GABA能或甘氨酸能神经元。Prdm13的缺失显著减少了GABA能和甘氨酸能的阿玛卡林，导致内网状层S2/S3边界突起束的特异性缺陷。Prdm13的强制表达可以诱导GABA能和甘氨酸能的无长突细胞，但不能诱导胆碱能的无长突细胞，而Prdm13的上游转录调控因子Ptf1a可以诱导所有这些亚型。此外，Prdm13基因缺陷的小鼠在视觉的空间、时间和对比敏感度方面表现出异常高的敏感性。总之，这些结果表明Prdm13调节着一组无长突细胞的发育，这种细胞新定义了一种无长突细胞亚型，以负向调节视觉敏感性。我们目前的研究为无长突细胞多样化的机制及其在视觉中的功能提供了新的见解。
Amacrine interneurons, which are highly diversified in morphological, neurochemical, and physiological features, play crucial roles in visual information processing in the retina. However, the specification mechanisms and functions in vision for each amacrine subtype are not well understood. We found that the Prdm13 transcriptional regulator is specifically expressed in developing and mature amacrine cells in the mouse retina. Most Prdm13-positive amacrine cells are Calbindin-and Calretinin-positive GABAergic or glycinergic neurons. Absence of Prdm13 significantly reduces GABAergic and glycinergic amacrines, resulting in a specific defect of the S2/S3 border neurite bundle in the inner plexiform layer. Forced expression of Prdm13 distinctively induces GABAergic and glycinergic amacrine cells but not cholinergic amacrine cells, whereas Ptf1a, an upstream transcriptional regulator of Prdm13, induces all of these subtypes. Moreover, Prdm13-deficient mice showed abnormally elevated spatial, temporal, and contrast sensitivities in vision. Together, these results show that Prdm13 regulates development of a subset of amacrine cells, which newly defines an amacrine subtype to negatively modulate visual sensitivities. Our current study provides new insights into mechanisms of the diversification of amacrine cells and their function in vision.