Bhattacharya Sumitra, Dooley Constance, Soto Frank, Madson Justin, Das Ani V, Ahmad Iqbal
Department Ophthalmology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Mol Cell Neurosci. 2004 Sep;27(1):32-43. doi: 10.1016/j.mcn.2004.05.004.
The cellular diversity of the mammalian retina is underpinned by multipotential neural progenitors that generate retinal neurons and glia with temporal and spatial specificity. It is thought, based on studies using a variety of approaches, that the fate of retinal progenitors is determined through interactions between temporally and spatially arrayed epigenetic cues with intrinsic factors that regulate the competence of cells to respond to such cues. Here, we demonstrate interactions between an intrinsic factor Ath3, a neural bHLH protein, and an extrinsic factor CNTF during the differentiation of the late retinal progenitors along the bipolar cell lineage. Expression of Ath3 is predominantly associated with the late stage of retinal histogenesis when bipolar cells are specified, and in adult it is detected in cells expressing bipolar cell-specific markers. We demonstrate that CNTF-induced bipolar cell differentiation is accompanied by an increase in levels of Ath3 transcripts and compromised when Ath3 expression is attenuated. Our study suggests that the influence of CNTF on the differentiation of late retinal progenitors is mediated through Ath3.
哺乳动物视网膜的细胞多样性由多能神经祖细胞支撑，这些祖细胞能以时间和空间特异性方式生成视网膜神经元和神经胶质细胞。基于使用多种方法进行的研究，人们认为视网膜祖细胞的命运是通过时间和空间排列的表观遗传线索与调节细胞对这些线索反应能力的内在因素之间的相互作用来决定的。在这里，我们展示了在晚期视网膜祖细胞沿双极细胞谱系分化过程中，内在因子Ath3（一种神经bHLH蛋白）与外在因子CNTF之间的相互作用。Ath3的表达主要与视网膜组织发生的晚期相关，此时双极细胞已确定，并且在成体中，在表达双极细胞特异性标志物的细胞中可检测到Ath3。我们证明，CNTF诱导的双极细胞分化伴随着Ath3转录本水平的增加，而当Ath3表达减弱时，这种分化会受到损害。我们的研究表明，CNTF对晚期视网膜祖细胞分化的影响是通过Ath3介导的。
