Targeted disruption of fibroblast growth factor (FGF) receptor 2 suggests a role for FGF signaling in pregastrulation mammalian development
Targeted disruption of fibroblast growth factor (FGF) receptor 2 suggests a role for FGF signaling in pregastrulation mammalian development
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DOI：
10.1073/pnas.95.9.5082
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发表时间：
1998-04-28
影响因子：
11.1
通讯作者：
Lonai, P
中科院分区：
文献类型：
--
作者：
Arman, E;Haffner-Krausz, R;Lonai, P
我们通过将neo盒引入IIIc配体结合外显子并通过删除编码其跨膜结构域和部分激酶I结构域的基因组DNA片段来破坏成纤维细胞生长因子（FGF）受体2（FGFR2）基因。获得了一个隐性胚胎致死突变。着床前发育正常，直至囊胚期。纯合突变胚胎在植入子宫腺窝的随机位置几小时后死亡，卵黄腔塌陷。突变囊胚在体外孵化、贴壁并形成一层滋养层巨细胞，但长时间培养后，内细胞团生长停止，无内脏内胚层形成，最后卵柱解体。因此，FGFR 2是植入和卵柱形成之间的早期植入后发育所必需的。我们认为FGFR2有助于内细胞团的生长、分化和维持，并提出了这种活性由FGFR2传递的FGF4信号介导的可能性。早期FGF信号在原肠胚形成前的发展中的作用作为一种可能的适应哺乳动物胚胎发生进行了讨论。
We disrupted the fibroblast growth factor (FGF) receptor 2 (FGFR2) gene by introducing a neo cassette into the IIIc ligand binding exon and by deleting a genomic DNA fragment encoding its transmembrane domain and part of its kinase I domain. A recessive embryonic lethal mutation was obtained. Preimplantation development was normal until the blastocyst stage. Homozygous mutant embryos died a few hours after implantation at a random position in the uterine crypt, with collapsed yolk cavity. Mutant blastocysts hatched, adhered, and formed a layer of trophoblast giant cells in vitro, but after prolonged culture, the growth of the inner cell mass stopped, no visceral endoderm formed, and finally the egg cylinder disintegrated. It follows that FGFR2 is required for early postimplantation development between implantation and the formation of the egg cylinder. We suggest that FGFR2 contributes to the outgrowth, differentiation, and maintenance of the inner cell mass and raise the possibility that this activity is mediated by FGF4 signals transmitted by FGFR2. The role of early FGF signaling in pregastrulation development as a possible adaptation to mammalian (amniote) embryogenesis is discussed.