NFI转录因子基因NFIA,Nfib和Nfix都富含晚期视网膜祖细胞,并且它们的损失已被证明保留了这些祖细胞,以牺牲后来产生的视网膜细胞类型为代价。他们是否在后来产生的命运的规范中扮演任何角色是未知的,但是其中一个表达,Nfia,在一个特定的无长突细胞类型可能亲密这样的作用。这里,Nfia-CKO小鼠(两性)进行评估,发现AII无长突细胞的大量选择性缺失。有,然而,2型视锥双极细胞(CBC)的部分减少,与AII细胞紧密相连。在AII细胞数量已经减少但在P10检测到2型CBC丢失之前,死亡细胞计数显示P7时Nfia-CKO视网膜显着增加。这些结果表明,Nfia在AII无长突细胞命运的规范中发挥作用,以及第二类CBCs对它们的依赖关系。将Nfia的有条件损失延迟到出生后的第一周不会改变AII细胞数量或分化,进一步表明其在AII细胞中的作用仅与它们的产生有关。使用ERG评估其损失的生理后果,发现振荡潜力被大大减弱。还检测到b波略有减少,归因于杆状双极细胞末端分布的改变,暗示AII无长突细胞在限制其分层中的作用。意义陈述转录因子NFIA被证明在单一类型的视网膜无长突细胞的规格中起关键作用,AII细胞。使用Nfia条件敲除小鼠来消除这种视网膜神经元,我们证明了两种选择性双极细胞对AII细胞的依赖性:杆状双极细胞的末端在内丛状层中分层,和一种类型的锥形双极细胞经历增强的细胞死亡。还评估了AII细胞丢失的生理后果,发现它们是视网膜电图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.