LIM-homeobox gene Lhx5 is required for normal development of Cajal-Retzius cells.
LIM-homeobox gene Lhx5 is required for normal development of Cajal-Retzius cells.
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DOI：
10.1523/jneurosci.5563-09.2010
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发表时间：
2010-08-04
期刊：
影响因子：
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通讯作者：
Zhao Y
中科院分区：
文献类型：
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作者：
Miquelajáuregui A;Varela-Echavarría A;Ceci ML;García-Moreno F;Ricaño I;Hoang K;Frade-Pérez D;Portera-Cailliau C;Tamariz E;De Carlos JA;Westphal H;Zhao Y
Cajal-Retzius（C-R）细胞通过分泌reelin在哺乳动物皮层的分层中起重要作用。这些神经元发育背后的遗传机制才刚刚开始被揭开。在这里，我们表明，两个密切相关的LIM同源框基因Lhx 1和Lhx 5的reelin+，细胞在小鼠端脑的各个区域或附近的C-R细胞产生的网站，包括皮质hem，隔膜/球后区和腹侧腭的地幔区域。而Lhx 5在所有这些reelin表达域中表达，Lhx 1优先在隔区和从外侧嗅区到尾内侧区的连续域中表达。Lhx 5基因切除导致新皮质原基、皮质边缘、隔区、嗅区和尾内侧端脑区的reelin+和p73+细胞减少。Lhx 5突变体中C-R细胞数量的总体减少伴随着尾侧端脑异位reelin+细胞簇的形成。基于分子标记的差异表达，并通过荧光细胞示踪在培养的胚胎中，我们定位的起源reelin+异位细胞簇的尾内侧端脑区域。我们还证实了存在一个正常的迁移流reelin+细胞从尾内侧区端脑嗅觉领域的野生型胚胎。这些结果揭示了Lhx 5在调节发育中前脑中C-R细胞的发育和正常分布中的复杂作用。
Cajal-Retzius (C-R) cells play important roles in the lamination of the mammalian cortex via reelin secretion. The genetic mechanisms underlying the development of these neurons have just begun to be unraveled. Here we show that two closely related LIM homeobox genes Lhx1 and Lhx5 are expressed in reelin+, cells in various regions in the mouse telencephalon at or adjacent to sites where the C-R cells are generated, including the cortical hem, the mantle region of the septal/retrobulbar area and the ventral pallium. Whereas Lhx5 is expressed in all of these reelin-expressing domains, Lhx1 is preferentially expressed in the septal area and in a continuous domain spanning from lateral olfactory region to caudomedial territories. Genetic ablation of Lhx5 results in decreased reelin+ and p73+ cells in the neocortical anlage, in the cortical hem and in the septal, olfactory, and caudomedial telencephalic regions. The overall reduction in number of C-R cells in Lhx5 mutants is accompanied by formation of ectopic reelin+ cell clusters at the caudal telencephalon. Based on differential expression of molecular markers and by fluorescent cell tracing in cultured embryos, we located the origin of reelin+ ectopic cell clusters at the caudomedial telencephalic region. We also confirmed the existence of a normal migration stream of reelin+ cells from the caudomedial area to telencephalic olfactory territories in wild-type embryos. These results reveal a complex role for Lhx5 in regulating the development and normal distribution of C-R cells in the developing forebrain.