Teneurin-3 regulates the generation of non-image-forming visual circuitry and responsiveness to light in the suprachiasmatic nucleus.
Teneurin-3 regulates the generation of non-image-forming visual circuitry and responsiveness to light in the suprachiasmatic nucleus.
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DOI：
10.1371/journal.pbio.3002412
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发表时间：
2023-12
期刊：
影响因子：
9.8
通讯作者：
Kolodkin, Alex L.
中科院分区：
文献类型：
--
作者：
Hunyara, John L.;Daly, K. M.;Torres, Katherine;Yurgel, Maria E.;Komal, Ruchi;Hattar, Samer;Kolodkin, Alex L.
视觉系统的功能取决于视网膜神经节细胞（RGC）轴突和其在大脑中的中央目标之间的精确连接的阐述。虽然在定义调节成像电路的组装和功能所需的RGC连接性的分子方面取得了一些进展，但令人惊讶的是，对内在光敏RGC（ipRGC）靶向非成像电路的主要组成部分所需的因素知之甚少：视交叉上核（SCN）。此外，在SCN内形成对昼夜节律行为至关重要的电路所需的分子是未知的。我们在这里观察到，粘附分子Tenerin-3（Tenm 3）是高度表达的血管活性肠肽（VIP）神经元位于SCN的核心区域。由于Tenm 3是哺乳动物视觉系统发育的其他方面所需的，我们研究Tenm 3在调节ipRGC-SCN连接和功能中的作用。我们的研究结果表明，Tenm 3负调节VIP和精氨酸加压素（AVP）神经元之间的关联SCN内，是必不可少的M1 ipRGC轴突神经支配SCN。具体而言，在Tenm 3-/-小鼠中，我们发现SCN的腹内侧神经支配减少。尽管有这种减少，Tenm 3-/-小鼠对光的敏感性更高，对相位提前的再夹带更快，这可能是由于VIP和AVP神经元之间的关联增加。这些数据表明，Tenm 3在阐述非图像形成视觉系统电路中起着关键作用，并且它影响小鼠对相位推进光刺激的反应。是什么使本质光敏视网膜神经节细胞靶向视交叉上核？这项研究表明，粘附分子teneurin-3在阐述这一电路中起着关键作用，并影响小鼠对相位推进光刺激的反应。
Visual system function depends upon the elaboration of precise connections between retinal ganglion cell (RGC) axons and their central targets in the brain. Though some progress has been made in defining the molecules that regulate RGC connectivity required for the assembly and function of image-forming circuitry, surprisingly little is known about factors required for intrinsically photosensitive RGCs (ipRGCs) to target a principal component of the non-image-forming circuitry: the suprachiasmatic nucleus (SCN). Furthermore, the molecules required for forming circuits critical for circadian behaviors within the SCN are not known. We observe here that the adhesion molecule teneurin-3 (Tenm3) is highly expressed in vasoactive intestinal peptide (VIP) neurons located in the core region of the SCN. Since Tenm3 is required for other aspects of mammalian visual system development, we investigate roles for Tenm3 in regulating ipRGC-SCN connectivity and function. Our results show that Tenm3 negatively regulates association between VIP and arginine vasopressin (AVP) neurons within the SCN and is essential for M1 ipRGC axon innervation to the SCN. Specifically, in Tenm3-/- mice, we find a reduction in ventro-medial innervation to the SCN. Despite this reduction, Tenm3-/- mice have higher sensitivity to light and faster re-entrainment to phase advances, probably due to the increased association between VIP and AVP neurons. These data show that Tenm3 plays key roles in elaborating non-image-forming visual system circuitry and that it influences murine responses to phase-advancing light stimuli. What enables intrinsically photosensitive retinal ganglion cells to target the suprachiasmatic nucleus? This study demonstrates that the adhesion molecule teneurin-3 plays a key role in elaborating this circuitry and influences murine responses to phase-advancing light stimuli.
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影响因子：
3.7
作者：
Dharmaratne N;Glendining KA;Young TR;Tran H;Sawatari A;Leamey CA
通讯作者：
Leamey CA
影响因子：
64.8
作者：
Hong, Weizhe;Mosca, Timothy J.;Luo, Liqun
通讯作者：
Luo, Liqun
影响因子：
3
作者：
Iyer R;Wang TA;Gillette MU
通讯作者：
Gillette MU
影响因子：
64.8
作者：
Berns DS;DeNardo LA;Pederick DT;Luo L
通讯作者：
Luo L
DOI：
10.1126/science.abg1774
发表时间：
2021-06-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Pederick DT;Lui JH;Gingrich EC;Xu C;Wagner MJ;Liu Y;He Z;Quake SR;Luo L
通讯作者：
Luo L