Neuroscience Research Institute, University of California, Santa Barbara, California 93106-5060
Neuroscience Research Institute, University of California, Santa Barbara, California 93106-5060.
J Neurosci. 2023 Dec 6;43(49):8367-8384. doi: 10.1523/JNEUROSCI.1099-23.2023.
The nuclear factor one (NFI) transcription factor genes , , and 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, , in a specific amacrine cell type may intimate such a role. Here, conditional knockout (-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 -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 in the specification of the AII amacrine cell fate and a dependency of the type 2 CBCs on them. Delaying the conditional loss of 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. 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 -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.
核因子一 (NFI) 转录因子基因 、 和 在晚期视网膜祖细胞中富集，其缺失已被证明以牺牲后期产生的视网膜细胞类型为代价保留这些祖细胞。它们是否在这些后期产生的命运的特化中发挥任何作用尚不清楚，但其中一种， ，在特定的无长突细胞类型中的表达可能暗示了这种作用。在这里，评估了 条件性敲除 (-CKO) 小鼠（雌雄同体），发现 AII 无长突细胞大量且基本上选择性缺失。然而，2 型视锥双极细胞 (CBC) 的数量减少，它们与 AII 细胞有丰富的相互连接。细胞死亡计数显示，在 AII 细胞数量减少后，但在 P10 时检测到 2 型 CBC 丢失之前，-CKO 视网膜在出生后第 7 天（P）出现显著增加。这些结果表明 对于 AII 无长突细胞命运的特化以及 2 型 CBC 对它们的依赖性具有重要作用。将 条件性缺失延迟到出生后的第一周不会改变 AII 细胞的数量或分化，这进一步表明它在 AII 细胞中的作用仅与它们的产生有关。使用 ERG 评估它们缺失的生理后果，发现振荡电位明显减少。还检测到 b 波略有降低，归因于视杆双极细胞末端的分布改变，暗示 AII 无长突细胞在限制它们的分层中起作用。转录因子 NFIA 被证明在单个视网膜无长突细胞类型，即 AII 细胞的特化中发挥关键作用。使用 -条件性敲除小鼠消除这种视网膜神经元群体，我们证明了两种选择性的双极细胞对 AII 细胞的依赖性；视杆双极细胞的末端在神经内丛状层中错位，一种类型的视锥双极细胞经历增强的细胞死亡。还评估了这种 AII 细胞缺失的生理后果，发现这些细胞是视网膜电图中振荡电位的主要贡献者。
