Poché Ross A, Kwan Kin Ming, Raven Mary A, Furuta Yasuhide, Reese Benjamin E, Behringer Richard R
Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
J Neurosci. 2007 Dec 19;27(51):14099-107. doi: 10.1523/JNEUROSCI.4046-07.2007.
Although much is known about the transcriptional regulation that coordinates retinal cell fate determination, very little is known about the developmental processes that establish the characteristic laminar architecture of the retina, in particular, the specification of neuronal positioning. The LIM class homeodomain transcription factor Lim1 (Lhx1) is expressed in postmitotic, differentiating, and mature retinal horizontal cells. We show that conditional ablation of Lim1 results in the ectopic localization of horizontal cells to inner aspects of the inner nuclear layer, among the retinal amacrine cells. The ectopic cells maintain a molecular phenotype consistent with horizontal cell identity; however, these neurons adopt a unique morphology more reminiscent of amacrine cells, including a dendritic arbor positioned within the inner plexiform layer. All other retinal cell populations appear unaltered. Our data suggest a model whereby Lim1 lies downstream of horizontal cell fate determination factors and functions cell autonomously to instruct differentiating horizontal cells to the appropriate laminar position in the developing retina. This study is the first to describe a cell type-specific genetic program that is essential for targeting a discrete retinal neuron population to the proper lamina.
尽管我们对协调视网膜细胞命运决定的转录调控了解很多，但对于建立视网膜特征性层状结构的发育过程，尤其是神经元定位的特化，却知之甚少。LIM类同源结构域转录因子Lim1（Lhx1）在有丝分裂后、分化中和成熟的视网膜水平细胞中表达。我们发现，条件性敲除Lim1会导致水平细胞异位定位到内核层内部、视网膜无长突细胞之间的区域。异位细胞维持与水平细胞身份一致的分子表型；然而，这些神经元呈现出一种独特的形态，更类似于无长突细胞，包括位于内网状层内的树突分支。所有其他视网膜细胞群体似乎未受影响。我们的数据提出了一个模型，即Lim1位于水平细胞命运决定因子的下游，并在细胞自主发挥作用，指导分化中的水平细胞在发育中的视网膜中到达合适的层位。这项研究首次描述了一种细胞类型特异性的遗传程序，该程序对于将离散的视网膜神经元群体靶向到正确的层至关重要。
