Transcriptome and proteome analysis of early embryonic mouse brain development
Transcriptome and proteome analysis of early embryonic mouse brain development
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DOI：
10.1002/pmic.200700724
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发表时间：
2008-03-01
期刊：
影响因子：
3.4
通讯作者：
Klose, Joachim
中科院分区：
文献类型：
--
作者：
Hartl, Daniela;Irmler, Martin;Klose, Joachim
小鼠胚胎脑的发育涉及多能祖细胞向神经元和神经胶质细胞的顺序分化。使用微阵列和大的2-DE，我们研究了小鼠大脑转录组和蛋白质组的胚胎天9.5，11.5，和13.5。在此发育期间，神经前体细胞从增殖转变为神经元分化。正如预期的那样，我们在研究的所有时间点之间检测到许多表达变化，但有趣的是，变化率在发育的2天内保持在相似的范围内。此外，基因产物的上调和下调在每个时间点都是平衡的，这在胚胎第16-18天也可以看到。我们假设，在胚胎发育过程中，基因表达变化的速率是相当恒定的，由于有限的细胞资源，如能量，空间和自由水。表达基因和蛋白质方面类似的复杂性表明，主导细胞分化的是相对浓度的变化，而不是基因产物数量的增加。一般而言，当前体细胞从增殖转换为神经元分化时（第9.5-11.5天），代谢和细胞周期相关基因产物的表达下调，而神经元特异性基因产物上调。详细的功能分析揭示了它们在分化相关过程中的意义，如肌动蛋白细胞骨架的重排以及Notch和Wnt信号通路。
Mouse embryonic brain development involves sequential differentiation of multipotent progenitors into neurons and glia cells. Using microarrays and large 2-DE, we investigated the mouse brain transcriptome and proteome of embryonic days 9.5, 11.5, and 13.5. During this developmental period, neural progenitor cells shift from proliferation to neuronal differentiation. As expected, we detected numerous expression changes between all time points investigated, but interestingly, the rate of alteration remained in a similar range within 2 days of development. Furthermore, up- and down-regulation of gene products was balanced at each time point which was also seen at embryonic days 16-18. We hypothesize that during embryonic development, the rate of gene expression alteration is rather constant due to limited cellular resources such as energy, space, and free water. A similar complexity in terms of expressed genes and proteins suggests that changes in relative concentrations rather than an increase in the number of gene products dominate cellular differentiation. In general, expression of metabolism and cell cycle related gene products was down-regulated when precursor cells switched from proliferation to neuronal differentiation (days 9.5-11.5), whereas neuron specific gene products were up-regulated. A detailed functional analysis revealed their implication in differentiation related processes such as rearrangement of the actin cytoskeleton as well as Notch- and Wnt-signaling pathways.