Mo Zeqian, Li Shengguo, Yang Xuejie, Xiang Mengqing
Center for Advanced Biotechnology and Medicine and Department of Pediatrics, UMDNJ-Robert Wood Johnson Medical School, 679 Hoes Lane, Piscataway, NJ 08854, USA.
Development. 2004 Apr;131(7):1607-18. doi: 10.1242/dev.01071. Epub 2004 Mar 3.
The mammalian retina contains numerous morphological and physiological subtypes of amacrine cells necessary for integrating and modulating visual signals presented to the output neurons. Among subtypes of amacrine cells grouped by neurotransmitter phenotypes, the glycinergic and gamma-aminobutyric acid (GABA)ergic amacrine cells constitute two major subpopulations. To date, the molecular mechanisms governing the specification of subtype identity of amacrine cells remain elusive. We report here that during mouse development, the Barhl2 homeobox gene displays an expression pattern in the nervous system that is distinct from that of its homologue Barhl1. In the developing retina, Barhl2 expression is found in postmitotic amacrine, horizontal and ganglion cells, while Barhl1 expression is absent. Forced expression of Barhl2 in retinal progenitors promotes the differentiation of glycinergic amacrine cells, whereas a dominant-negative form of Barhl2 has the opposite effect. By contrast, they exert no effect on the formation of GABAergic neurons. Moreover, misexpressed Barhl2 inhibits the formation of bipolar and Müller glial cells, indicating that Barhl2 is able to function both as a positive and negative regulator, depending on different types of cells. Taken together, our data suggest that Barhl2 may function to specify the identity of glycinergic amacrine cells from competent progenitors during retinogenesis.
哺乳动物的视网膜包含众多形态和生理亚型的无长突细胞，这些细胞对于整合和调节传递给输出神经元的视觉信号至关重要。在按神经递质表型分类的无长突细胞亚型中，甘氨酸能和γ-氨基丁酸（GABA）能无长突细胞构成了两个主要亚群。迄今为止，控制无长突细胞亚型身份特化的分子机制仍不清楚。我们在此报告，在小鼠发育过程中，Barhl2同源盒基因在神经系统中的表达模式与其同源物Barhl1不同。在发育中的视网膜中，Barhl2表达见于有丝分裂后的无长突细胞、水平细胞和神经节细胞，而Barhl1不表达。在视网膜祖细胞中强制表达Barhl2可促进甘氨酸能无长突细胞的分化，而Barhl2的显性负性形式则有相反的作用。相比之下，它们对GABA能神经元的形成没有影响。此外，错误表达的Barhl2会抑制双极细胞和Müller胶质细胞的形成，这表明Barhl2能够根据不同类型的细胞发挥正向和负向调节作用。综上所述，我们的数据表明，Barhl2可能在视网膜发育过程中，从有能力的祖细胞中指定甘氨酸能无长突细胞的身份。
