Weisinger Karen, Wilkinson David G, Sela-Donenfeld Dalit
Koret School of Veterinary Medicine, Hebrew University, Faculty of Agriculture, Food and Environmental Quality Sciences, P.O. Box 12, Rehovot 76100, Israel.
Dev Biol. 2008 Dec 15;324(2):213-25. doi: 10.1016/j.ydbio.2008.09.005. Epub 2008 Sep 18.
A network of molecular interactions is required in the developing vertebrate hindbrain for the formation and anterior-posterior patterning of the rhombomeres. FGF signaling is required in this network to upregulate the expression of the Krox20 and Kreisler segmentation genes, but little is known of how FGF gene expression is regulated in the hindbrain. We show that the dynamic expression of FGF3 in chick hindbrain segments and boundaries is similar to that of the BMP antagonist, follistatin. Consistent with a regulatory relationship between BMP signaling and FGF3 expression, we find that an increase in BMP activity due to blocking of follistatin translation by morpholino antisense oligonucleotides or overexpression of BMP results in strong inhibition of FGF3 expression. Conversely, addition of follistatin leads to an increase in the level of FGF3 expression. Furthermore, the segmental inhibition of BMP activity by follistatin is required for the expression of Krox20, Hoxb1 and EphA4 in the hindbrain. In addition, we show that the maintenance of FGF3 gene expression requires FGF activity, suggestive of an autoregulatory loop. These results reveal an antagonistic relationship between BMP activity and FGF3 expression that is required for correct segmental gene expression in the chick hindbrain, in which follistatin enables FGF3 expression by inhibiting BMP activity.
在发育中的脊椎动物后脑，菱脑节的形成和前后模式化需要一个分子相互作用网络。该网络中FGF信号传导对于上调Krox20和Kreisler节段基因的表达是必需的，但对于后脑FGF基因表达如何被调控却知之甚少。我们发现，FGF3在鸡后脑节段和边界的动态表达与BMP拮抗剂卵泡抑素相似。与BMP信号传导和FGF3表达之间的调控关系一致，我们发现，通过吗啉代反义寡核苷酸阻断卵泡抑素翻译或BMP过表达导致BMP活性增加，从而强烈抑制FGF3表达。相反，添加卵泡抑素会导致FGF3表达水平增加。此外，卵泡抑素对BMP活性的节段性抑制是后脑Krox20、Hoxb1和EphA4表达所必需的。另外，我们表明FGF3基因表达的维持需要FGF活性，提示存在一个自调节环。这些结果揭示了BMP活性与FGF3表达之间的拮抗关系，这是鸡后脑正确节段基因表达所必需的，其中卵泡抑素通过抑制BMP活性使FGF3得以表达。
