Hutson Mary R, Zhang Ping, Stadt Harriett A, Sato Asako K, Li Yin-Xiong, Burch Jarrett, Creazzo Tony L, Kirby Margaret L
Neonatal-Perinatal Research Institute, Division of Neonatology, Department of Pediatrics, Box 3179, Duke University Medical Center, Durham, NC 27710, USA.
Dev Biol. 2006 Jul 15;295(2):486-97. doi: 10.1016/j.ydbio.2006.02.052. Epub 2006 Jun 12.
Morphogenesis of the cardiac arterial pole is dependent on addition of myocardium and smooth muscle from the secondary heart field and septation by cardiac neural crest cells. Cardiac neural crest ablation results in persistent truncus arteriosus and failure of addition of myocardium from the secondary heart field leading to malalignment of the arterial pole with the ventricles. Previously, we have shown that elevated FGF signaling after neural crest ablation causes depressed Ca2+ transients in the primary heart tube. We hypothesized that neural crest ablation results in elevated FGF8 signaling in the caudal pharynx that disrupts secondary heart field development. In this study, we show that FGF8 signaling is elevated in the caudal pharynx after cardiac neural crest ablation. In addition, treatment of cardiac neural crest-ablated embryos with FGF8b blocking antibody or an FGF receptor blocker rescues secondary heart field myocardial development in a time- and dose-dependent manner. Interestingly, reduction of FGF8 signaling in normal embryos disrupts myocardial secondary heart field development, resulting in arterial pole malalignment. These results indicate that the secondary heart field myocardium is particularly sensitive to FGF8 signaling for normal conotruncal development, and further, that cardiac neural crest cells modulate FGF8 signaling in the caudal pharynx.
心脏动脉极的形态发生依赖于来自第二心脏场的心肌和平滑肌的添加以及心脏神经嵴细胞的分隔。心脏神经嵴消融导致永存动脉干以及无法从第二心脏场添加心肌，从而导致动脉极与心室排列不齐。此前，我们已经表明神经嵴消融后FGF信号升高会导致原始心管中Ca2+瞬变降低。我们推测神经嵴消融会导致尾侧咽部FGF8信号升高，从而破坏第二心脏场的发育。在本研究中，我们表明心脏神经嵴消融后尾侧咽部的FGF8信号升高。此外，用FGF8b阻断抗体或FGF受体阻滞剂处理心脏神经嵴消融的胚胎能以时间和剂量依赖的方式挽救第二心脏场心肌的发育。有趣的是，正常胚胎中FGF8信号的降低会破坏心肌第二心脏场的发育，导致动脉极排列不齐。这些结果表明，第二心脏场心肌对正常圆锥动脉干发育的FGF8信号特别敏感，而且，心脏神经嵴细胞调节尾侧咽部的FGF8信号。
