Firnberg Nicole, Neubüser Annette
Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, Vienna, A-1030, Austria.
Dev Biol. 2002 Jul 15;247(2):237-50. doi: 10.1006/dbio.2002.0696.
Fgf8 is required for normal development of the nasal region. Here, we have used a candidate approach to identify genes that are induced in chick nasal mesenchyme in response to FGF signaling. Using an explant culture system, we show that expression of the transcription factors Tbx2, Erm, Pea3, and Pax3, but not Pax7, in nasal mesenchyme is regulated by ectodermal signals in a stage-dependent manner. Using beads soaked in recombinant FGF protein and an FGF receptor antagonist, we furthermore demonstrate that FGF signaling is necessary and sufficient for expression of Tbx2, Erm, Pea3, and Pax3, but has no effect on Pax7 expression. We also show that, within the nasal mesenchyme, competence to respond to FGF signaling is initially widespread and uniform but becomes restricted to regions normally exposed to FGF at later stages of development, coincident with changes in FGF receptor expression. Finally, we provide evidence that FGF8 also regulates Erm and Pea3 expression in the nasal placodes. Together, these results identify Tbx2, Erm, Pea3, and Pax3 as downstream targets of FGF signaling in the facial area and suggest that these genes may mediate some of the effects of FGF8 during development of the nasal region.
Fgf8是鼻区正常发育所必需的。在此,我们采用候选基因方法来鉴定在鸡胚鼻间充质中因FGF信号传导而被诱导的基因。利用外植体培养系统,我们发现鼻间充质中转录因子Tbx2、Erm、Pea3和Pax3(而非Pax7)的表达受外胚层信号以阶段依赖性方式调控。通过浸泡重组FGF蛋白的珠子和FGF受体拮抗剂,我们进一步证明FGF信号传导对于Tbx2、Erm、Pea3和Pax3的表达是必要且充分的,但对Pax7表达没有影响。我们还表明,在鼻间充质内,对FGF信号传导作出反应的能力最初广泛且均匀,但在发育后期变得局限于正常暴露于FGF的区域,这与FGF受体表达的变化相一致。最后,我们提供证据表明FGF8也调节鼻基板中Erm和Pea3的表达。总之,这些结果确定Tbx2、Erm、Pea3和Pax3为面部区域FGF信号传导的下游靶点,并表明这些基因可能介导FGF8在鼻区发育过程中的一些作用。