BARHL2 differentially regulates the development of retinal amacrine and ganglion neurons.
BARHL2 differentially regulates the development of retinal amacrine and ganglion neurons.
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DOI：
10.1523/jneurosci.5237-08.2009
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发表时间：
2009-04-01
期刊：
影响因子：
--
通讯作者：
Gan L
中科院分区：
文献类型：
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作者：
Ding Q;Chen H;Xie X;Libby RT;Tian N;Gan L
通过转录调控，同源结构域蛋白质的BarH家族在细胞命运规范、细胞分化、迁移和存活中发挥重要作用。Barhl 2是Barh基因家族的成员，在视网膜神经节细胞（RGC）、无长突细胞（AC）和水平细胞中表达。在此，为了研究Barhl 2在视网膜发育中的作用，产生了Barhl 2缺陷型小鼠。对Barhl 2缺陷型视网膜中AC亚型的分析表明，Barhl 2在AC亚型确定中起关键作用。在Barhl 2缺失的视网膜中观察到甘氨酸能和GABA能AC的显著减少以及胆碱能AC数量的显著增加。Barhl 2对于RGC的正常补体的发育也是至关重要的。Barhl 2缺陷导致在发育过程中经历凋亡的RGCs增加35%。遗传分析显示，Barhl 2在Atoh 7-Pou 4f 3调节途径的下游发挥作用，并调节RGCs的成熟和/或存活。因此，BARHL 2似乎在视网膜发育中具有许多作用，包括调节神经元亚型的特化、分化和存活。
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.