Kulesh Bridget, Reese Benjamin E, Keeley Patrick W
Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA, United States.
Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, United States.
Front Neuroanat. 2022 Aug 19;16:944706. doi: 10.3389/fnana.2022.944706. eCollection 2022.
Multiple factors regulate the differentiation of neuronal morphology during development, including interactions with afferents, targets, and homotypic neighbors, as well as cell-intrinsic transcriptional regulation. Retinal bipolar cells provide an exemplary model system for studying the control of these processes, as there are 15 transcriptionally and morphologically distinct types, each extending their dendritic and axonal arbors in respective strata within the synaptic layers of the retina. Here we have examined the role of the transcription factor in the control of the morphological differentiation of one type of cone bipolar cell (CBC), the Type 7 cell. We confirm selective expression of SOX5 in this single bipolar cell type, emerging at the close of the first post-natal week, prior to morphological differentiation. Conditional knockout mice were generated by crossing a bipolar cell-specific -expressing line with mice carrying floxed alleles, as well as the reporter which labels Type 7 CBCs. Loss of SOX5 was confirmed in the bipolar cell stratum, in GFP+ Type 7 cells. Such SOX5-deficient Type 7 cells differentiate axonal and dendritic arbors that are each reduced in areal extent. The axonal arbors exhibit sprouting in the inner plexiform layer (IPL), thereby extending their overall radial extent, while the dendritic arbors connect with fewer cone pedicles in the outer plexiform layer, showing an increase in the average number of dendritic contacts at each pedicle. SOX5-deficient Type 7 CBCs should therefore exhibit smaller receptive fields derived from fewer if now hyper-innervated pedicles, transmitting their signals across a broader depth through the IPL.
在发育过程中,多种因素调节神经元形态的分化,包括与传入神经、靶细胞和同型邻居的相互作用,以及细胞内在的转录调控。视网膜双极细胞为研究这些过程的控制提供了一个典型的模型系统,因为有15种转录和形态上不同的类型,每种类型在视网膜突触层的各自层中延伸其树突和轴突分支。在这里,我们研究了转录因子在一种视锥双极细胞(CBC)即7型细胞形态分化控制中的作用。我们证实SOX5在这种单一的双极细胞类型中选择性表达,在出生后第一周结束时出现,早于形态分化。通过将双极细胞特异性表达系与携带floxed等位基因的小鼠以及标记7型CBC的报告基因小鼠杂交,产生了条件性敲除小鼠。在双极细胞层的GFP + 7型细胞中证实了SOX5的缺失。这种缺乏SOX5的7型细胞分化出的轴突和树突分支在面积范围上都减小了。轴突分支在内网状层(IPL)中表现出芽生,从而扩大了它们的整体径向范围,而树突分支在外网状层中与较少的视锥细胞蒂相连,显示每个蒂处树突接触的平均数量增加。因此,缺乏SOX5的7型CBC应该表现出来自更少(如果现在是超支配的)视锥细胞蒂的更小的感受野,通过IPL在更宽的深度上传递它们的信号。