Focal adhesion kinase is essential for cardiac looping and multichamber heart formation.

Focal adhesion kinase is essential for cardiac looping and multichamber heart formation.
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DOI:
10.1002/dvg.20650
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发表时间:
2010-08
期刊:
影响因子:
1.5
通讯作者:
Taylor, Joan M.
Taylor, Joan M.
中科院分区:
生物学4区
文献类型:
--
作者:
Doherty, Jason T.;Conlon, Frank L.;Mack, Christopher P.;Taylor, Joan M.

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粘着斑激酶(FAK)是发育过程中基质和生长因子诱导的信号传导的关键介质。妊娠中期小鼠心肌细胞限制性FAK缺失导致心室间隔和心脏致密化受损然而,FAK是否调节早期心源性步骤仍然未知。为了探索FAK在多室心脏形成中的作用,我们利用反义吗啉代耗尽非洲爪蟾中的FAK。爪蟾FAK变形表现出受损的心脏发生,明显的心包水肿,并致死蝌蚪阶段。心脏标志物基因表达的时空评估显示,FAK是不必要的中线迁移,分化,融合的心脏前体,或线性心管的形成。然而,肌细胞增殖显着减少FAK变形的心管,这些管未能进行适当的循环形态发生。总的来说,我们的数据表明,FAK在室生长和循环形态发生中起着重要作用,可能是由成纤维细胞生长因子(可能还有其他)心肌营养因子刺激的。
Focal adhesion kinase (FAK) is a critical mediator of matrix- and growth factor-induced signaling during development. Myocyte-restricted FAK deletion in mid-gestation mice results in impaired ventricular septation and cardiac compaction. However, whether FAK regulates early cardiogenic steps remains unknown. To explore a role for FAK in multi-chambered heart formation, we utilized anti-sense morpholinos to deplete FAK in Xenopus laevis. Xenopus FAK morphants exhibited impaired cardiogenesis, pronounced pericardial edema, and lethality by tadpole stages. Spatial-temporal assessment of cardiac marker gene expression revealed that FAK was not necessary for midline migration, differentiation, fusion of cardiac precursors, or linear heart tube formation. However, myocyte proliferation was significantly reduced in FAK morphant heart tubes and these tubes failed to undergo proper looping morphogenesis. Collectively our data imply that FAK plays an essential role in chamber outgrowth and looping morphogenesis likely stimulated by fibroblast growth factors (and possibly other) cardiotrophic factors.
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