Role of Fabp7, a downstream gene of Pax6, in the maintenance of neuroepithelial cells during early embryonic development of the rat cortex
Role of Fabp7, a downstream gene of Pax6, in the maintenance of neuroepithelial cells during early embryonic development of the rat cortex
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DOI：
10.1523/jneurosci.2512-05.2005
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发表时间：
2005-10-19
影响因子：
5.3
通讯作者：
Osumi, N
中科院分区：
文献类型：
--
作者：
Arai, Y;Funatsu, N;Osumi, N
Pax6是一种转录因子，在大脑发育过程中起着关键的功能作用。Pax6通过转录调控神经原蛋白2(Neurogenin2，Ngn2)基因促进神经元分化，尽管Pax6在神经发生开始之前就在增殖的神经上皮细胞中表达。在这里，我们通过芯片分析发现，脂肪酸结合蛋白(FABP)家族的成员Fabp7(BLBP/B-FABP)是Pax6突变大鼠胚胎脑中下调的基因(rSey(2)/rSey(2))。定量聚合酶链式反应证实Fabp7的表达明显降低。从胚胎第10.5天(E10.5)到胚胎14.5天，野生型大鼠胚胎中Fabp7的时空表达模式与Pax6相似，在rSey2/rSey2皮质中未检测到Fabp7的表达。在E10.5的野生型小鼠胚胎(相当于E12.5大鼠)中，Fabp7的表达模式与在大鼠胚胎中的表达模式不同，而在Sey/Sey小鼠胚胎中的表达没有变化。外源Pax6的过表达主要诱导早期皮质原基中Fabp7的异位表达，而不是Ngn2的异位表达。有趣的是，通过电穿孔Fabp7小干扰RNA来下调FABP7的功能，严重地抑制了细胞的增殖，但促进了神经元的分化。我们的结论是，Fabp7是发育中的大鼠皮质中Pax6转录因子的下游基因，在皮质发育的早期对神经上皮细胞的维持是必不可少的。
Pax6 is a transcription factor with key functional roles in the developing brain. Pax6 promotes neuronal differentiation via transcriptional regulation of the Neurogenin2 (Ngn2) gene, although Pax6 expression appears in proliferating neuroepithelial cells before the onset of neurogenesis. Here, we identified Fabp7 (BLBP/B-FABP), a member of the fatty acid-binding protein (FABP) family, as a downregulated gene in the embryonic brain of Pax6 mutant rat (rSey(2)/rSey(2)) by microarray analysis. Marked reduction of Fabp7 expression was confirmed by quantitative PCR. Spatiotemporal expression patterns of Fabp7 in the wild-type rat embryos from embryonic day 10.5 (E10.5) to E14.5 were similar to those of Pax6, and expression of Fabp7 was undetectable in the rSey2/rSey2 cortex. The expression pattern of Fabp7 in the wild- type mouse embryo at E10.5 (corresponding to E12.5 rat) was different from that in the rat embryo, and no change of expression was observed in the Sey/Sey mouse embryo. Overexpression of exogenous Pax6 mainly induced ectopic expression of Fabp7, rather than of Ngn2, in the early cortical primordium. Interestingly, knocking-down FABP7 function by electroporation of Fabp7 small interfering RNA severely curtailed cell proliferation but promoted neuronal differentiation. We conclude that Fabp7 is a downstream gene of Pax6 transcription factor in the developing rat cortex and essential for maintenance of neuroepithelial cells during early cortical development.