Nfia Is Critical for AII Amacrine Cell Production: Selective Bipolar Cell Dependencies and Diminished ERG.
Nfia Is Critical for AII Amacrine Cell Production: Selective Bipolar Cell Dependencies and Diminished ERG.
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DOI：
10.1523/jneurosci.1099-23.2023
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发表时间：
2023-12-06
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影响因子：
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核因子一（NFI）转录因子基因Nfia、Nfib和Nfix都在晚期视网膜祖细胞中富集，并且它们的缺失已显示以牺牲后来产生的视网膜细胞类型为代价保留这些祖细胞。它们是否在这些后来产生的命运的规范中发挥任何作用尚不清楚，但其中之一，Nfia，在特定的无长突细胞类型中的表达可能暗示了这样的作用。在此，评估了Nfia条件性敲除（Nfia-CKO）小鼠（两种性别），发现大量且很大程度上选择性缺乏AII无长突细胞。然而，2型锥体双极细胞（CBCs）部分减少，与AII细胞密切相关。死亡细胞的计数显示在出生后第7天（P）Nfia-CKO视网膜中显著增加，在AII细胞数量已经减少之后，但在P10检测到的2型CBC损失之前。这些结果表明Nfia在AII无长突细胞命运的规范中的作用以及2型CBC对它们的依赖性。将Nfia的条件性丧失延迟至出生后第一周并没有改变AII细胞的数量或分化，进一步表明其在AII细胞中的作用仅与其产生相关。他们的损失的生理后果进行了评估，使用ERG，发现振荡电位大大减少。还检测到b波的轻微减少，这归因于杆双极细胞的末端分布的改变，暗示AII无长突细胞在约束其分层中的作用。转录因子NFIA在单一类型的视网膜无长突细胞（AII细胞）的特化中起关键作用。使用Nfia条件性基因敲除小鼠，以消除这一群体的视网膜神经元，我们证明了两个选择性的双极细胞依赖于AII细胞;杆双极细胞的终端成为错误分层的内丛状层，和一种类型的锥双极细胞经历了增强的细胞死亡。还评估了AII细胞的这种损失的生理后果，发现细胞是视网膜电图中振荡电位的主要贡献者。
The nuclear factor one (NFI) transcription factor genes Nfia, Nfib, and Nfix are all enriched in late-stage retinal progenitor cells, and their loss has been shown to retain these progenitors at the expense of later-generated retinal cell types. Whether they play any role in the specification of those later-generated fates is unknown, but the expression of one of these, Nfia, in a specific amacrine cell type may intimate such a role. Here, Nfia conditional knockout (Nfia-CKO) mice (both sexes) were assessed, finding a massive and largely selective absence of AII amacrine cells. There was, however, a partial reduction in type 2 cone bipolar cells (CBCs), being richly interconnected to AII cells. Counts of dying cells showed a significant increase in Nfia-CKO retinas at postnatal day (P)7, after AII cell numbers were already reduced but in advance of the loss of type 2 CBCs detected by P10. Those results suggest a role for Nfia in the specification of the AII amacrine cell fate and a dependency of the type 2 CBCs on them. Delaying the conditional loss of Nfia to the first postnatal week did not alter AII cell number nor differentiation, further suggesting that its role in AII cells is solely associated with their production. The physiological consequences of their loss were assessed using the ERG, finding the oscillatory potentials to be profoundly diminished. A slight reduction in the b-wave was also detected, attributed to an altered distribution of the terminals of rod bipolar cells, implicating a role of the AII amacrine cells in constraining their stratification. SIGNIFICANCE STATEMENT The transcription factor NFIA is shown to play a critical role in the specification of a single type of retinal amacrine cell, the AII cell. Using an Nfia–conditional knockout mouse to eliminate this population of retinal neurons, we demonstrate two selective bipolar cell dependencies on the AII cells; the terminals of rod bipolar cells become mis-stratified in the inner plexiform layer, and one type of cone bipolar cell undergoes enhanced cell death. The physiological consequence of this loss of the AII cells was also assessed, finding the cells to be a major contributor to the oscillatory potentials in the electroretinogram.
影响因子：
4.3
作者：
Kulesh, Bridget;Bozadjian, Rachel;Parisi, Ryan J. J.;Leong, Stephanie A. A.;Kautzman, Amanda G. G.;Reese, Benjamin E. E.;Keeley, Patrick W. W.
通讯作者：
Keeley, Patrick W. W.
小鼠视网膜的杆途径中的细胞数，细胞比和发育可塑性。
影响因子：
2.4
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