A p38 MAPK-CREB pathway functions to pattern mesoderm in Xenopus
A p38 MAPK-CREB pathway functions to pattern mesoderm in Xenopus
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DOI：
10.1016/j.ydbio.2008.07.010
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发表时间：
2008-10-01
影响因子：
2.7
通讯作者：
Bengal, Eyal
中科院分区：
文献类型：
--
作者：
Keren, Aviad;Keren-Politansky, Anat;Bengal, Eyal
背腹模式是由信号中心分泌拮抗形成信号梯度的形态原而指定的。然而，形态梯度如何在细胞内转化为命运决定在很大程度上仍是未知的。在这里，我们报道了p38MAPK和CREB在中胚层图案化中沿着背腹轴的作用。我们发现，CREB(S133)的磷酸化形式沿中胚层背侧-腹轴呈梯度分布，并且p38MAPK通路介导了CREB的磷酸化。CREB基因的敲除阻止了Spemann组织者的Chordin表达和中胚层背化，而激活的CREB-VP16嵌合体的异位表达诱导了Chordin的表达并使中胚层背化。在胚胎中高水平表达p38激活剂、MKK6E或CREB-VP16可将腹侧中胚层转化为背侧组织中心。P38MAPK和CREB在母体Wnt/β-catenin以及组织特异性基因siamois和goosecid下游发挥作用。在低表达水平，MKK6E诱导侧向基因的表达，而不诱导背侧基因的表达。CREB或p38man活性的丧失使腹侧同源盒基因vent1能够扩展到背缘区域，阻止Xmyf5的横向表达。总体而言，这些数据表明，背侧-腹侧中胚层的模式受到沿轴线的不同p38/CREB活动的调节。(C)2008 Elsevier Inc.保留所有权利。
Dorsal-ventral patterning is specified by signaling centers secreting antagonizing morphogens that form a signaling gradient. Yet, how morphogen gradient is translated intracellularly into fate decisions remains largely unknown. Here, we report that p38 MAPK and CREB function along the dorsal-ventral axis in mesoderm patterning. We find that the phosphorylated form of CREB (S133) is distributed in a gradient along the dorsal-ventral mesoderm axis and that the p38 MAPK pathway mediates the phosphorylation of CREB. Knockdown of CREB prevents chordin expression and mesoderm dorsalization by the Spemann organizer, whereas ectopic expression of activated CREB-VP16 chimera induces chordin expression and dorsalizes mesoderm. Expression of high levels of p38 activator, MKK6E or CREB-VP16 in embryos converts ventral mesoderm into a dorsal organizing center. p38 MAPK and CREB function downstream of maternal Wnt/beta-catenin and the organizer-specific genes siamois and goosecoid. At low expression levels, MKK6E induces expression of lateral genes without inducing the expression of dorsal genes. Loss of CREB or p38 MAN activity enables the expansion of the ventral homeobox gene vent1 into the dorsal marginal region, preventing the lateral expression of Xmyf5. Overall, these data indicate that dorsal-ventral mesoderm patterning is regulated by differential p38/CREB activities along the axis. (c) 2008 Elsevier Inc. All rights reserved.