L3/Lhx8 is involved in the determination of cholinergic or GABAergic cell fate
L3/Lhx8 is involved in the determination of cholinergic or GABAergic cell fate
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DOI：
10.1111/j.1471-4159.2005.03261.x
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发表时间：
2005-08-01
影响因子：
4.7
通讯作者：
Wanaka, A
中科院分区：
文献类型：
--
作者：
Manabe, T;Tatsumi, K;Wanaka, A
LIM同源框转录因子家族参与哺乳动物中枢神经系统发育的许多过程。L3，也称为Lhx 8（L3/Lhx 8），是最近鉴定的LIM同源框基因家族的成员，并且选择性地在内侧神经节隆起（MGE）中表达。我们以前的研究表明，L3/Lhx 8-null小鼠特别缺乏基底前脑胆碱能神经元。在这项研究中，我们减少L3/Lhx 8功能的小鼠神经母细胞瘤细胞系，Neuro 2a（N2 a），使用L3/Lhx 8靶向的小干扰RNA（siRNA）产生的H1.2启动子驱动的载体。每个细胞的胆碱能标记物水平降低，而标记物阳性细胞的数量没有减少。有趣的是，GABA能标记物表达和GABA能细胞的数量在分化中的L3/Lhx 8敲低的N2 a中显著增加。这些结果表明，L3/Lhx 8的可能性，参与在基底前脑发育过程中的神经元群体中的递质表型（GABA能或胆碱能细胞的命运）的确定。
The LIM homeobox family of transcription factors is involved in many processes during the development of the mammalian central nerves system. L3, also called Lhx8 (L3/Lhx8), is a recently identified member of the LIM homeobox gene family and is selectively expressed in the medial ganglionic eminence (MGE). Our previous study demonstrated that L3/Lhx8-null mice specifically lacked cholinergic neurons in the basal forebrain. In this study, we reduced L3/Lhx8 function in the murine neuroblastoma cell line, Neuro2a (N2a), using L3/ Lhx8-targeted small interfering RNA (siRNA) produced by H1.2 promoter-driven vector. The levels of cholinergic markers per cell were diminished without a reduction in the number of marker-positive cells. Intriguingly, GABAergic marker expression and the number of GABAergic cells were dramatically increased in the differentiating L3/Lhx8-knockdown N2a. These results suggest the possibility that L3/Lhx8 is involved in the determination of transmitter phenotypes (GABAergic or cholinergic cell fate) in a population of neurons during basal forebrain development.