Röttinger Eric, Saudemont Alexandra, Duboc Véronique, Besnardeau Lydia, McClay David, Lepage Thierry
UMR 7009 CNRS, Université Pierre et Marie Curie (Paris 6 Océanologique, 06230 Villefranche sur mer, France.
Development. 2008 Jan;135(2):353-65. doi: 10.1242/dev.014282. Epub 2007 Dec 12.
The sea urchin embryo is emerging as an attractive model to study morphogenetic processes such as directed migration of mesenchyme cells and cell sheet invagination, but surprisingly, few of the genes regulating these processes have yet been characterized. We present evidence that FGFA, the first FGF family member characterized in the sea urchin, regulates directed migration of mesenchyme cells, morphogenesis of the skeleton and gastrulation during early development. We found that at blastula stages, FGFA and a novel putative FGF receptor are expressed in a pattern that prefigures morphogenesis of the skeletogenic mesoderm and that suggests that FGFA is one of the elusive signals that guide migration of primary mesenchyme cells (PMCs). We first show that fgfA expression is correlated with abnormal migration and patterning of the PMCs following treatments that perturb specification of the ectoderm along the oral-aboral and animal-vegetal axes. Specification of the ectoderm initiated by Nodal is required to restrict fgfA to the lateral ectoderm, and in the absence of Nodal, fgfA is expressed ectopically throughout most of the ectoderm. Inhibition of either FGFA, FGFR1 or FGFR2 function severely affects morphogenesis of the skeleton. Furthermore, inhibition of FGFA and FGFR1 signaling dramatically delays invagination of the archenteron, prevents regionalization of the gut and abrogates formation of the stomodeum. We identified several genes acting downstream of fgfA in these processes, including the transcription factors pea3 and pax2/5/8 and the signaling molecule sprouty in the lateral ectoderm and SM30 and SM50 in the primary mesenchyme cells. This study identifies the FGF signaling pathway as an essential regulator of gastrulation and directed cell migration in the sea urchin embryo and as a key player in the gene regulatory network directing morphogenesis of the skeleton.
海胆胚胎正成为研究形态发生过程（如间充质细胞的定向迁移和细胞层内陷）的一个有吸引力的模型，但令人惊讶的是，调控这些过程的基因中很少有被鉴定出来的。我们提供证据表明，FGFA是海胆中首个被鉴定的FGF家族成员，在早期发育过程中调控间充质细胞的定向迁移、骨骼形态发生和原肠胚形成。我们发现，在囊胚期，FGFA和一种新的假定FGF受体以一种预示着造骨中胚层形态发生的模式表达，这表明FGFA是引导初级间充质细胞（PMC）迁移的难以捉摸的信号之一。我们首先表明，在扰乱沿口 - 反口轴和动物 - 植物轴的外胚层特化的处理后，fgfA的表达与PMC的异常迁移和模式形成相关。由Nodal启动的外胚层特化是将fgfA限制在外侧外胚层所必需的，并且在没有Nodal的情况下，fgfA在大部分外胚层中异位表达。抑制FGFA、FGFR1或FGFR2的功能会严重影响骨骼的形态发生。此外，抑制FGFA和FGFR1信号会显著延迟原肠的内陷，阻止肠道的区域化并消除口凹的形成。我们在这些过程中鉴定了几个在fgfA下游起作用的基因，包括外侧外胚层中的转录因子pea3和pax2/5/8以及信号分子sprouty，以及初级间充质细胞中的SM30和SM50。这项研究确定FGF信号通路是海胆胚胎中原肠胚形成和定向细胞迁移的重要调节因子，也是指导骨骼形态发生的基因调控网络中的关键参与者。
