Xu R H, Ault K T, Kim J, Park M J, Hwang Y S, Peng Y, Sredni D, Kung H f
Intramural Research Support Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland, 21702, USA.
Dev Biol. 1999 Apr 15;208(2):352-61. doi: 10.1006/dbio.1999.9205.
In adult vertebrates, fibroblast growth factor (FGF) synergizes with many hematopoietic cytokines to stimulate the proliferation of hematopoietic progenitors. In vertebrate development, the FGF signaling pathway is important in the formation of some derivatives of ventroposterior mesoderm. However, the function of FGF in the specification of the embryonic erythropoietic lineage has remained unclear. Here we address the role of FGF in the specification of the erythropoietic lineage in the Xenopus embryo. We report that ventral injection of embryonic FGF (eFGF) mRNA at as little as 10 pg at the four-cell stage suppresses ventral blood island (VBI) formation, whereas expression of the dominant negative form of the FGF receptor in the lateral mesoderm, where physiologically no blood tissue is formed, results in a dramatic expansion of the VBI. Similar results were observed in isolated ventral marginal zones and animal caps. Bone morphogenetic protein-4 (BMP-4) is known to induce erythropoiesis in the Xenopus embryo. Therefore, we examined how the BMP-4 and FGF signaling pathways might interact in the decision of ventral mesoderm to form blood. We observed that eFGF inhibits BMP-4-induced erythropoiesis by differentially regulating expression of the BMP-4 downstream effectors GATA-2 and PV.1. GATA-2, which stimulates erythropoiesis, is suppressed by FGF. PV.1, which we demonstrate to inhibit blood development, is enhanced by FGF. Additionally, PV.1 and GATA-2 negatively regulate transcription of each other. Thus, BMP-4 induces two transcription factors which have opposing effects on blood development. The FGF and BMP-4 signaling pathways interact to regulate the specification of the erythropoietic lineage.
在成年脊椎动物中，成纤维细胞生长因子（FGF）与多种造血细胞因子协同作用，刺激造血祖细胞的增殖。在脊椎动物发育过程中，FGF信号通路在腹后中胚层某些衍生物的形成中起重要作用。然而，FGF在胚胎红细胞生成谱系特化中的功能仍不清楚。在此，我们研究了FGF在非洲爪蟾胚胎红细胞生成谱系特化中的作用。我们报告，在四细胞期腹侧注射低至10 pg的胚胎FGF（eFGF）mRNA可抑制腹侧血岛（VBI）的形成，而在生理上不形成血液组织的外侧中胚层中表达FGF受体的显性负性形式，则会导致VBI显著扩大。在分离的腹侧边缘区和动物帽中也观察到了类似结果。已知骨形态发生蛋白-4（BMP-4）可诱导非洲爪蟾胚胎中的红细胞生成。因此，我们研究了BMP-4和FGF信号通路在腹侧中胚层形成血液的决定过程中可能如何相互作用。我们观察到，eFGF通过差异调节BMP-4下游效应因子GATA-2和PV.1的表达来抑制BMP-4诱导的红细胞生成。刺激红细胞生成的GATA-2被FGF抑制。我们证明可抑制血液发育的PV.1被FGF增强。此外，PV.1和GATA-2相互负调控转录。因此，BMP-4诱导了两种对血液发育具有相反作用的转录因子。FGF和BMP-4信号通路相互作用以调节红细胞生成谱系的特化。
