Shifts in the vascular endothelial growth factor isoforms result in transcriptome changes correlated with early neural stem cell proliferation and differentiation in mouse forebrain.
Shifts in the vascular endothelial growth factor isoforms result in transcriptome changes correlated with early neural stem cell proliferation and differentiation in mouse forebrain.
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DOI：
10.1002/dneu.22130
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发表时间：
2014-01
影响因子：
3
通讯作者：
Darland, Diane C.
中科院分区：
文献类型：
--
作者：
Cain, Jacob T.;Berosik, Matthew A.;Snyder, Stephanie D.;Crawford, Natalie F.;Nour, Shirin I.;Schaubhut, Geoffrey J.;Darland, Diane C.
神经干细胞（NSC）的命运决定的调节是至关重要的，从多细胞的哺乳动物前脑神经上皮的过渡到多层的新皮层。前脑的发育需要协调的血管投资以及NSC分化。血管内皮生长因子A（VEGF）已被证明是一个多效性基因，其多种蛋白异构体在神经血管系统中调节广泛的作用。为了检验VEGF亚型（120、164和188）是正常前脑发育所需的假设，我们分析了表达特定VEGF亚型、Vegf 120、VegfF 188或Vegf 120/188组合的小鼠的前脑转录组。转录组分析鉴定了胚胎第9.5天前脑中差异表达的基因，该时间点在端脑中神经上皮急剧扩张和血管投资之前。荟萃分析确定了与染色体水平修饰，细胞命运调控和VEGF同种型小鼠中改变的神经发生相关的基因途径。基于这些基因网络的变化，我们预测NSC群体将在前脑发育的后期受到影响。在E11.5端脑中，我们定量了有丝分裂细胞[磷酸化组蛋白H3（pHH 3）阳性]和中间祖细胞（Tbr 2/Eomes阳性），观察了这些群体的定量和定性变化。我们观察到皮质分层在P0的质的变化，特别是与Ctip 2阳性细胞在第V层。结果确定了一套基因和功能基因网络，可用于进一步剖析VEGF在调节NSC分化的作用和NSC命运决定的下游后果。
Regulation of neural stem cell (NSC) fate decisions is critical during the transition from a multicellular mammalian forebrain neuroepithelium to the multi-layered neocortex. Forebrain development requires coordinated vascular investment alongside NSC differentiation. Vascular endothelial growth factor A (Vegf) has proven to be a pleiotrophic gene whose multiple protein isoforms regulate a broad range of effects in neurovascular systems. To test the hypothesis that the Vegf isoforms (120, 164, and 188) are required for normal forebrain development, we analyzed the forebrain transcriptome of mice expressing specific Vegf isoforms, Vegf120, VegfF188, or a combination of Vegf120/188. Transcriptome analysis identified differentially expressed genes in embryonic day (E) 9.5 forebrain, a time point preceding dramatic neuroepithelial expansion and vascular investment in the telencephalon. Meta-analysis identified gene pathways linked to chromosome-level modifications, cell fate regulation, and neurogenesis that were altered in Vegf isoform mice. Based on these gene network shifts, we predicted that NSC populations would be affected in later stages of forebrain development. In the E11.5 telencephalon, we quantified mitotic cells [Phospho-Histone H3 (pHH3)-positive] and intermediate progenitor cells (Tbr2/Eomes-positive), observing quantitative and qualitative shifts in these populations. We observed qualitative shifts in cortical layering at P0, particularly with Ctip2-positive cells in layer V. The results identify a suite of genes and functional gene networks that can be used to further dissect the role of Vegf in regulating NSC differentiation and downstream consequences for NSC fate decisions.
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DOI：
10.1073/pnas.1002285107
发表时间：
2010-07-20
影响因子：
11.1
作者：
Bedogni, Francesco;Hodge, Rebecca D.;Hevner, Robert F.
通讯作者：
Hevner, Robert F.
影响因子：
16.2
作者：
Hevner, RF;Shi, LM;Rubenstein, JLR
通讯作者：
Rubenstein, JLR
DOI：
10.1111/j.1460-9568.2008.06475.x
发表时间：
2008-10
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Bayatti N;Sarma S;Shaw C;Eyre JA;Vouyiouklis DA;Lindsay S;Clowry GJ
通讯作者：
Clowry GJ
影响因子：
3.4
作者：
Hartl, Daniela;Irmler, Martin;Klose, Joachim
通讯作者：
Klose, Joachim
影响因子：
64.5
作者：
ERICSON, J;MUHR, J;EDLUND, T
通讯作者：
EDLUND, T