Ding Qian, Chen Hui, Xie Xiaoling, Libby Richard T, Tian Ning, Gan Lin
University of Rochester Eye Institute, University of Rochester, Rochester, New York 14642, USA.
J Neurosci. 2009 Apr 1;29(13):3992-4003. doi: 10.1523/JNEUROSCI.5237-08.2009.
Through transcriptional regulations, the BarH family of homeodomain proteins play essential roles in cell fate specification, cell differentiation, migration, and survival. Barhl2, a member of the Barh gene family, is expressed in retinal ganglion cells (RGCs), amacrine cells (ACs), and horizontal cells. Here, to investigate the role of Barhl2 in retinal development, Barhl2-deficient mice were generated. Analysis of AC subtypes in Barhl2-deficient retinas suggests that Barhl2 plays a critical role in AC subtype determination. A significant reduction of glycinergic and GABAergic ACs with a substantial increase in the number of cholinergic ACs was observed in Barhl2-null retinas. Barhl2 is also critical for the development of a normal complement of RGCs. Barhl2 deficiency resulted in a 35% increase in RGCs undergoing apoptosis during development. Genetic analysis revealed that Barhl2 functions downstream of the Atoh7-Pou4f3 regulatory pathway and regulates the maturation and/or survival of RGCs. Thus, BARHL2 appears to have numerous roles in retinal development, including regulating neuronal subtype specification, differentiation, and survival.
通过转录调控，同源结构域蛋白的BarH家族在细胞命运决定、细胞分化、迁移和存活中发挥着重要作用。Barhl2是Barh基因家族的成员之一，在视网膜神经节细胞（RGCs）、无长突细胞（ACs）和水平细胞中表达。在此，为了研究Barhl2在视网膜发育中的作用，构建了Barhl2基因敲除小鼠。对Barhl2基因敲除视网膜中AC亚型的分析表明，Barhl2在AC亚型确定中起关键作用。在Barhl2基因敲除的视网膜中观察到甘氨酸能和GABA能ACs显著减少，而胆碱能ACs数量大幅增加。Barhl2对正常数量的RGCs的发育也至关重要。Barhl2缺陷导致发育过程中经历凋亡的RGCs增加35%。遗传分析表明，Barhl2在Atoh7-Pou4f3调控途径的下游发挥作用，并调节RGCs的成熟和/或存活。因此，BARHL2似乎在视网膜发育中具有多种作用，包括调节神经元亚型的确定、分化和存活。
