Zebrafish Tbx16 regulates intermediate mesoderm cell fate by attenuating Fgf activity.
Zebrafish Tbx16 regulates intermediate mesoderm cell fate by attenuating Fgf activity.
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DOI：
10.1016/j.ydbio.2013.08.018
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发表时间：
2013-11-01
影响因子：
2.7
通讯作者：
Kane, Donald A.
中科院分区：
文献类型：
--
作者：
Warga, Rachel M.;Mueller, Rachel L.;Ho, Robert K.;Kane, Donald A.
斑马鱼的原肾细胞、红细胞和干内皮细胞的祖细胞都起源于腹侧中胚层，并且经常彼此共享谱系，这表明它们的初始模式是有联系的。先前的研究表明，spt突变胚胎，tbx16基因功能缺陷，不能产生红细胞，但保留正常数量的内皮细胞和肾原细胞。我们在这里报道，与野生型相比，spt突变体在所有类型的早期血液中都存在缺陷，内皮细胞更少，肾原细胞更多。体内细胞追踪实验显示，spt突变体的血液和内皮几乎完全起源于中胚层的背侧，而前肾和尾巴则起源于中胚层的背侧和腹侧。综上所述，这些发现提示了后路模式可能存在的缺陷。与此相一致的是，基因表达分析表明，spt突变体躯干和尾部的中胚层衍生物获得了更多的后侧同一性。属于Fgf、Wnt和Bmp家族的分泌信号分子被认为是后中胚层的模式因子。进一步的研究表明，Fgf和Wnt信号在spt原肠胚的非轴向区升高。通过操纵Fgf信号，我们发现Fgfs既促进肾原命运，又抑制血液和内皮命运。我们得出结论，Tbx16通过降低Fgf活性在调节中胚层命运平衡中发挥重要作用。
Progenitors of the zebrafish pronephros, red blood and trunk endothelium all originate from the ventral mesoderm and often share lineage with one another, suggesting that their initial patterning is linked. Previous studies have shown that spadetail (spt) mutant embryos, defective in tbx16 gene function, fail to produce red blood cells, but retain the normal number of endothelial and pronephric cells. We report here that spt mutants are deficient in all the types of early blood, have fewer endothelial cells as well as far more pronephric cells compared to wildtype. In vivo cell tracing experiments reveal that blood and endothelium originate in spt mutants almost exclusively from the dorsal mesoderm whereas, pronephros and tail originate from both dorsal and ventral mesoderm. Together these findings suggest possible defects in posterior patterning. In accord with this, gene expression analysis show that mesodermal derivatives within the trunk and tail of spt mutants have acquired more posterior identity. Secreted signaling molecules belonging to the Fgf, Wnt and Bmp families have been implicated as patterning factors of the posterior mesoderm. Further investigation demonstrate that Fgf and Wnt signaling are elevated throughout the nonaxial region of the spt gastrula. By manipulating Fgf signaling we show that Fgfs both promote pronephric fate and repress blood and endothelial fate. We conclude that Tbx16 plays an important role in regulating the balance of intermediate mesoderm fates by attenuating Fgf activity.
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