Wang H F, Liu F C
Institute of Neuroscience, National Yang-Ming University, Taipei, 112, Republic of, Taiwan, China.
Neuroscience. 2001;103(4):999-1016. doi: 10.1016/s0306-4522(00)00590-x.
LIM homeodomain transcription factors play crucial roles in determining diverse aspects of neuronal development both in vertebrates and invertebrates. In the present study, we studied the expression pattern of Islet-1 (Isl-1), a member of the LIM homeodomain protein family, in the rat striatum during development. The developmental expression of Isl-1 in the striatum is highly dynamic and complex in terms of spatial and temporal regulation. The reverse transcription-polymerase chain reaction and ribonuclease protection assays demonstrated that Isl-1 messenger RNA was expressed in the developing striatum. The immunocytochemical study of Isl-1 protein expression showed that there were prominent mediolateral and caudorostral Isl-1 gradients in the developing striatum. Numerous Isl-1-positive cells appeared in the medial mantle zone of the developing striatal proper, and they co-expressed the postmitotic neuronal marker, microtubule-associated protein 2. The numbers of Isl-1-positive cells were decreased from the medial to the lateral regions, so that there were only a few Isl-1-positive cells scattered in the lateral striatum. These scattered Isl-1-positive cells were doubly labeled with tyrosine kinase receptor A and choline acetyltransferase, which indicated that they were cholinergic neurons. The Isl-1 gradients were most prominent in the embryonic day 18 and 20 striatum. With increases of time, the Isl-1 gradients were gradually reduced, and the gradients disappeared by postnatal day 7. Despite the general down-regulation of striatal Isl-1, a few Isl-1-positive cells were sustained into the adult striatum in which Isl-1 was nearly exclusively expressed by all cholinergic neurons and vice versa. Our study suggests that Isl-1 is likely to be initially expressed by postmitotic cholinergic precursors and some, if not all, non-cholinergic precursors in the developing striatum. During the progression of striatal differentiation, Isl-1 is down-regulated in non-cholinergic cells, but is sustained in cholinergic cells. The developmental restriction of Isl-1 to cholinergic neurons in the striatum may represent a novel mechanism by which LIM homeodomain proteins specify specific cell types in the striatum during development.
LIM 同源域转录因子在脊椎动物和无脊椎动物神经元发育的多个方面都起着关键作用。在本研究中，我们研究了 LIM 同源域蛋白家族成员胰岛 1（Islet-1，Isl-1）在大鼠纹状体发育过程中的表达模式。就空间和时间调控而言，Isl-1 在纹状体中的发育表达具有高度的动态性和复杂性。逆转录聚合酶链反应和核糖核酸酶保护分析表明，Isl-1 信使核糖核酸在发育中的纹状体中表达。对 Isl-1 蛋白表达的免疫细胞化学研究表明，在发育中的纹状体中存在明显的中外侧和尾嘴侧 Isl-1 梯度。许多 Isl-1 阳性细胞出现在发育中的纹状体本体的内侧套层区，并且它们共同表达有丝分裂后神经元标记物微管相关蛋白 2。Isl-1 阳性细胞的数量从内侧区域到外侧区域逐渐减少，因此外侧纹状体中仅散布着少数 Isl-1 阳性细胞。这些散布的 Isl-1 阳性细胞用酪氨酸激酶受体 A 和胆碱乙酰转移酶进行双重标记，这表明它们是胆碱能神经元。Isl-1 梯度在胚胎第 18 天和第 20 天的纹状体中最为明显。随着时间的增加，Isl-1 梯度逐渐减小，并且在出生后第 7 天梯度消失。尽管纹状体中 Isl-1 总体下调，但仍有一些 Isl-1 阳性细胞持续存在于成年纹状体中，其中 Isl-1 几乎仅由所有胆碱能神经元表达，反之亦然。我们的研究表明，Isl-1 可能最初由发育中的纹状体中有丝分裂后的胆碱能前体以及一些（如果不是全部）非胆碱能前体表达。在纹状体分化过程中，Isl-1 在非胆碱能细胞中下调，但在胆碱能细胞中持续存在。Isl-1 在纹状体中对胆碱能神经元的发育限制可能代表了一种新机制，通过该机制 LIM 同源域蛋白在发育过程中指定纹状体中的特定细胞类型。
