Delgado Irene, Domínguez-Frutos Elena, Schimmang Thomas, Ros Maria A
Departamento de Anatomía y Biología Celular, Universidad de Cantabria, C/Herrera Oria s/n, E-39011 Santander, Spain.
Dev Dyn. 2008 Mar;237(3):649-58. doi: 10.1002/dvdy.21452.
Here we analyze limb development after the conditional inactivation of Fgf8 from the epiblast, using the previously described MORE (Mox2Cre) line. This line drives variable mosaic recombination of a floxed Fgf8 allele, resulting in a small proportion of AER cells that maintain Fgf8 expression. The phenotype of Mox2Cre;Fgf8 limbs is most similar to that of Msx2Cre;Fgf8 forelimbs, indicating that a small but durable expression of FGF8 is equivalent to an early normal, but transitory, expression. This functional equivalence likely relies on the subsequent Fgf4 upregulation that buffers the differences in the pattern of Fgf8 expression between the two conditional mutants. The molecular analysis of Mox2Cre;Fgf8 limbs shows that, despite Fgf4 upregulation, they develop under reduced FGF signaling. These limbs also exhibit an abnormal area of cell death at the anterior forelimb autopod, overlapping with an ectopic domain of Bmp7 expression, which can explain the abnormal morphogenesis of the anterior autopod.
在此，我们利用先前描述的MORE（Mox2Cre）品系，分析了胚外中胚层中Fgf8条件性失活后的肢体发育情况。该品系驱动了Fgf8条件性等位基因的可变镶嵌重组，导致一小部分顶外胚层嵴（AER）细胞维持Fgf8表达。Mox2Cre;Fgf8肢体的表型与Msx2Cre;Fgf8前肢的表型最为相似，这表明FGF8少量但持久的表达等同于早期正常但短暂的表达。这种功能等效性可能依赖于随后Fgf4的上调，从而缓冲了两个条件性突变体之间Fgf8表达模式的差异。对Mox2Cre;Fgf8肢体的分子分析表明，尽管Fgf4上调，但它们在FGF信号传导减弱的情况下发育。这些肢体在前肢远端部还表现出异常的细胞死亡区域，与Bmp7表达的异位区域重叠，这可以解释前肢远端部的异常形态发生。
