Pax6-5a Promotes Neuronal Differentiation of Murine Embryonic Stem Cells
Pax6-5a Promotes Neuronal Differentiation of Murine Embryonic Stem Cells
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DOI：
10.1248/bpb.32.999
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发表时间：
2009-06-01
影响因子：
2
通讯作者：
Nishina, Hiroshi
中科院分区：
文献类型：
--
作者：
Shimizu, Nao;Watanabe, Hajime;Nishina, Hiroshi
Pax 6基因高度保守，对眼睛发育非常重要。脊椎动物主要产生两种选择性剪接的Pax 6同种型，Pax 6和Pax 6 -5a。Pax 6 -5a与Pax 6的不同之处在于存在由外显子5a编码的14个额外的氨基酸。这些额外的氨基酸出现在Pax 6配对结构域中，从而影响其DNA结合特性。然而，对Pax 6 -5a的生理功能知之甚少。在这里，我们建立了小鼠胚胎干细胞（ES）细胞系中的人Pax 6或Pax 6 -5a亚型的表达是负控制四环素。我们报道，与Pax 6表达相反，Pax 6 -5a表达强烈诱导ES细胞分化为神经元。此外，使用DNA微阵列分析，我们已经确定了转录因子基本螺旋环螺旋结构域包含，类b2（bHLHb 2）在Pax 6 - 5a表达的ES细胞。我们的Pax 6异构体表达ES细胞系可以作为有用的模型，用于识别Pax 6调节的基因，这些基因对神经发生和/或眼睛发育很重要。
Pax6 genes are highly conserved and important for eye development. Vertebrates predominantly produce two alternatively spliced Pax6 isoforms, Pax6 and Pax6-5a. Pax6-5a differs from Pax6 by the presence of 14 additional amino acids encoded by exon 5a. These additional amino acids occur in the Pax6 paired domain and thus influence its DNA-binding properties. However, little is known about Pax6-5a's physiological functions. Here we establish murine embryonic stem (ES) cell lines in which expression of either the human Pax6 or Pax6-5a isoform is negatively controlled by tetracycline. We report that, in contrast to Pax6 expression, Pax6-5a expression strongly induces ES cells to differentiate into neurons. Moreover, using DNA microarray analysis, we have identified the transcription factor basic helix loop-helix domain containing, class b2 (bHLHb2) in Pax6-5a-expressing ES cells. Our Pax6 isoform-expressing ES cell lines may serve as useful models for identifying Pax6-regulated genes that are important for neurogenesis and/or eye development.