Which FGF ligands are involved in lens induction?
Which FGF ligands are involved in lens induction?
复制标题
哪些 FGF 配体参与晶状体诱导？
DOI：
10.1016/j.ydbio.2009.11.009
复制
发表时间：
2010
影响因子：
2.7
通讯作者：
Lang,RichardA
中科院分区：
文献类型：
--
作者：
Smith,AprilN;Radice,Glenn;Lang,RichardA
Hans Spemann（Spemann，1901）的视杯消融实验引入了胚胎诱导的概念，并确定假定视网膜提供透镜发育所需的信号。从那时起，透镜诱导一直是发育生物学家希望了解诱导信号的分子机制的青睐的主题。关于透镜诱导的遗传调控已经有了很多了解，图1总结了一些进展。转录因子Pax 6是中心参与。这两者都是必要的（Ashery-Padan等人，2000; Collinson等人，2000）和充分（Altmann等人，1997; Chow等人，1999）用于透镜发育，并由成纤维细胞生长因子（FGF）诱导（Faber等人，2001; Gotoh等人，2004）和骨形态发生蛋白7（BMP 7）（Wawersik等，1999）早期透镜形成所需的信号通路。Meis和Six家族转录因子也通过它们对Pax 6基因的外胚层增强子的作用而涉及透镜诱导（Zhang et al.，2002; Liu等人，2006年）。Sry家族转录因子Sox 2参与透镜发育（Kamachi et al.，2001; Kondoh等人，2004）并且在基板前阶段具有与Pax 6基本平行的功能（Smith等人，2009年）。Sox 2被BMP 4上调，BMP 4是参与透镜诱导的第一个信号配体（Furuta和Hogan，1998）。在最近的分析中，Grainger小组提供了证据，证明广泛表达的转录因子Otx 2与局部表达的Notch途径转录调节因子无毛抑制因子（Su（H））合作，以上调FoxE 3的表达并限定透镜基板外胚层（Ogino et al.，2008年）。由于Su（H）依赖于在视泡中表达的Notch途径配体Delta 2，这是从经典研究中预期的透镜诱导信号传导类型的实例。在BMP和Notch信号传导途径的情况下，有证据表明特定的配体-受体对参与透镜诱导（Furuta和Hogan，1998; Wawersik等人，1999; Ogino等人，2008年）。相比之下，尽管有大量证据表明FGF信号转导参与透镜和视网膜诱导，但迄今为止还没有记录到必需的配体。显性负性FGF受体在透镜基板中的表达（Faber等，2001）和FGF受体衔接子FRS 2 α的突变体分析（Gotoh等，2004）都表明假定的透镜细胞中的FGF反应是发育进行所必需的。鸡中的外植体研究还表明FGF途径参与相互信号传导（晶状体-视网膜）（Nguyen和Arnheiter，2000），这与FRS 2 α突变小鼠假定视网膜中磷酸-ERK免疫反应性降低一致（Gotoh et al.，2004年）。透镜发育的后期阶段也需要FGF信号传导。透镜纤维细胞分化也可以用显性阴性或Ig融合FGF受体抑制（Chow等人，1995;罗宾逊等人，1995 a; Govindarajan和Overbeek，2001）。此外，FGF配体可在培养物或体内增强纤维细胞分化（McAb和Chamberlain，1989;罗宾逊等人，1995年b）。在透镜系统中进行的实验也证明了FGF信号传导系统中的冗余。在一场基因之旅中，
The optic cup ablation experiments of Hans Spemann (Spemann, 1901) introduced the concept of embryonic induction and established that presumptive retina provided signals required for lens development. Since then, lens induction has been a favored subject for developmental biologists wishing to understand the molecular mechanisms of inductive signaling. Much has been learned about the genetic regulation of lens induction and Fig. 1 summarizes some of the advances. The transcription factor Pax6 is centrally involved. It is both necessary (Ashery-Padan et al., 2000; Collinson et al., 2000) and sufficient (Altmann et al., 1997; Chow et al., 1999) for lens development and is induced by the fibroblast growth factor (FGF)(Faber et al., 2001; Gotoh et al., 2004) and bone morphogenetic protein 7 (BMP7)(Wawersik et al., 1999) signaling pathways that are required for early lens formation. Meis and Six family transcription factors have also been implicated in lens induction through their action at the Ectoderm Enhancer of the Pax6 gene (Zhang et al., 2002; Liu et al., 2006). The Sry family transcription factor Sox2 is involved in lens development (Kamachi et al., 2001; Kondoh et al., 2004) and has an essential, parallel function to Pax6 at pre-placodal stages (Smith et al., 2009). Sox2 is up-regulated by BMP4, the first signaling ligand to be implicated in lens induction (Furuta and Hogan, 1998). In a recent analysis, the Grainger group has provided evidence that the broadly expressed transcription factor Otx2 cooperates with the locally expressed Notch pathway transcriptional regulator suppressor of hairless (Su (H)) to up-regulate expression of FoxE3 and define lens placode ectoderm (Ogino et al., 2008). Since Su (H) is dependent on the Notch pathway ligand Delta2 that is expressed in the optic vesicle, this is an example of the type of lens induction signaling that would be anticipated from classical studies.In the case of the BMP and Notch signaling pathways, there is evidence for the involvement of particular ligand–receptor pairs in lens induction (Furuta and Hogan, 1998; Wawersik et al., 1999; Ogino et al., 2008). By contrast, despite the extensive evidence for FGF signaling involvement in lens and retinal induction, no essential ligands have thus far been documented. Expression of dominantnegative FGF receptors in the lens placode (Faber et al., 2001) and analysis of mutants for the FGF receptor adaptor FRS2α (Gotoh et al., 2004) both suggested that the FGF response in cells of the presumptive lens was required for development to proceed. Explant studies in the chick have also implicated the FGF pathway in reciprocal signaling (lens-to-retina)(Nguyen and Arnheiter, 2000) and this is consistent with reduced phospho-ERK immunoreactivity in the presumptive retina of FRS2α mutant mice (Gotoh et al., 2004). Later stages of lens development also require FGF signaling. Lens fiber cell differentiation can also be suppressed with dominant-negative, or Ig-fusion FGF receptors (Chow et al., 1995; Robinson et al., 1995a; Govindarajan and Overbeek, 2001). Furthermore, fiber cell differentiation can be enhanced by FGF ligands either in culture or in vivo (McAvoy and Chamberlain, 1989; Robinson et al., 1995b). Experiments performed in the lens system have also demonstrated redundancy in the FGF signaling system. In a genetic tour-de-force,