ERK1 and ERK2 MAPK are key regulators of distinct gene sets in zebrafish embryogenesis.
ERK1 and ERK2 MAPK are key regulators of distinct gene sets in zebrafish embryogenesis.
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DOI：
10.1186/1471-2164-9-196
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发表时间：
2008-04-28
期刊：
影响因子：
4.4
通讯作者：
Spaink HP
中科院分区：
文献类型：
--
作者：
Krens SF;Corredor-Adámez M;He S;Snaar-Jagalska BE;Spaink HP
MAPK信号蛋白参与了许多真核细胞过程和信号网络。然而，由于潜在的冗余，这些蛋白质中的大多数在脊椎动物发育中的特定功能仍然难以捉摸。例如，ERK1和ERK2的上游激活途径高度相似，而且它们的许多已知下游靶点也是共同的。相比之下，小鼠和斑马鱼的研究表明，这两种ERK在细胞增殖、致癌转化和发育中扮演着不同的角色。进一步研究的一个主要瓶颈是，对这些激酶的体内下游信号转导知之甚少。基于基因芯片的ERK1和ERK2敲除斑马鱼胚胎在早期胚胎发育不同阶段的基因表达谱分析结果表明，在基因本体论分析中，特定的基因表达特征集显示出明显的差异。为了预测这些基因的功能，利用GenMAPP程序构建了斑马鱼在早期胚胎发育过程中所特有的电子信号通路。对获得的转录组信号在BMP、FGFNodal和Wnt途径中进行了分析。整装原位杂交实验证实了ERK1和ERK2基因敲除处理对调控中胚层发育的关键通路的下游效应。基因本体论分析表明，ERK1和ERK2针对共同和不同的基因集合，证实了这些激酶在胚胎发育过程中击倒表型的差异和不同的作用。对于ERK1，我们确定了与背腹模式和随后的胚胎细胞迁移有关的特定基因。对于ERK2，我们确定了与细胞迁移、中内胚层分化和图案化有关的基因。ERK2在中胚层和内胚层形成的启动、维持和模式形成中的特定功能已在生物学上得到证实。
The MAPK signaling proteins are involved in many eukaryotic cellular processes and signaling networks. However, specific functions of most of these proteins in vertebrate development remain elusive because of potential redundancies. For instance, the upstream activation pathways for ERK1 and ERK2 are highly similar, and also many of their known downstream targets are common. In contrast, mice and zebrafish studies indicate distinct roles for both ERKs in cellular proliferation, oncogenic transformation and development. A major bottleneck for further studies is that relatively little is known of in vivo downstream signaling specific for these kinases. Microarray based gene expression profiling of ERK1 and ERK2 knockdown zebrafish embryos at various stages of early embryogenesis resulted in specific gene expression signature sets that showed pronounced differences in gene ontology analyses. In order to predict functions of these genes, zebrafish specific in silico signaling pathways involved in early embryogenesis were constructed using the GenMAPP program. The obtained transcriptome signatures were analyzed in the BMP, FGF, Nodal and Wnt pathways. Predicted downstream effects of ERK1 and ERK2 knockdown treatments on key pathways responsible for mesendoderm development were confirmed by whole mount in situ hybridization experiments. The gene ontology analyses showed that ERK1 and ERK2 target common and distinct gene sets, confirming the difference in knockdown phenotypes and diverse roles for these kinases during embryogenesis. For ERK1 we identified specific genes involved in dorsal-ventral patterning and subsequent embryonic cell migration. For ERK2 we identified genes involved in cell-migration, mesendoderm differentiation and patterning. The specific function of ERK2 in the initiation, maintenance and patterning of mesoderm and endoderm formation was biologically confirmed.
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影响因子：
56.9
作者：
Behrens, J;Jerchow, BA;Birchmeier, W
通讯作者：
Birchmeier, W
影响因子：
--
作者：
Lloyd AC
通讯作者：
Lloyd AC
影响因子：
3
作者：
Beisvag V;Jünge FK;Bergum H;Jølsum L;Lydersen S;Günther CC;Ramampiaro H;Langaas M;Sandvik AK;Laegreid A
通讯作者：
Laegreid A
影响因子：
2.5
作者：
KIMMEL, CB;BALLARD, WW;SCHILLING, TF
通讯作者：
SCHILLING, TF
影响因子：
4.6
作者：
Bissonauth, Vickram;Roy, Sophie;Charron, Jean
通讯作者：
Charron, Jean