FoxF is essential for FGF- induced migration of heart progenitor cells in the ascidian Ciona intestinalis
FoxF is essential for FGF- induced migration of heart progenitor cells in the ascidian Ciona intestinalis
复制标题
DOI：
10.1242/dev.010140
复制
发表时间：
2007-09-15
期刊：
影响因子：
4.6
通讯作者：
Christiaen, Lionel
中科院分区：
文献类型：
--
作者：
Beh, Jeni;Shi, Weiyang;Christiaen, Lionel
心脏发育需要精确协调形态发生运动与渐进的细胞命运特化和分化。在海鞘胚胎中，FGF/MAPK介导的转录因子Ets 1/2的激活是心脏组织特化和细胞迁移所必需的。我们发现FoxF是心脏前体中响应FGF信号传导而被激活的第一个基因之一。我们鉴定了FoxF最小心脏增强子，并使用顺反互补试验表明Ets 1/2可以与FoxF增强子在体内相互作用。接下来，我们发现FoxF功能是细胞迁移所需的下游和平行于FGF/MAPK/Ets级联反应。此外，我们证明了FoxF的显性负性形式的靶向表达抑制细胞迁移，但不抑制心脏分化，从而产生了一个引人注目的表型：在青少年体腔内异位位置的跳动心脏。总之，我们的研究结果表明，FoxF是FGF信号转导的直接靶点，主要参与心脏细胞迁移的调节。
Heart development requires precise coordination of morphogenetic movements with progressive cell fate specification and differentiation. In ascidian embryos, FGF/MAPK-mediated activation of the transcription factor Ets1/2 is required for heart tissue specification and cell migration. We found that FoxF is one of the first genes to be activated in heart precursors in response to FGF signaling. We identified the FoxF minimal heart enhancer and used a cis-trans complementation test to show that Ets1/2 can interact with the FoxF enhancer in vivo. Next, we found that FoxF function is required downstream and in parallel to the FGF/MAPK/Ets cascade for cell migration. In addition, we demonstrated that targeted expression of a dominant-negative form of FoxF inhibits cell migration but not heart differentiation, resulting in a striking phenotype: a beating heart at an ectopic location within the body cavity of juveniles. Taken together, our results indicate that FoxF is a direct target of FGF signaling and is predominantly involved in the regulation of heart cell migration.