The incomplete inactivation of Fgf8 in the limb ectoderm affects the morphogenesis of the anterior autopod through BMP-mediated cell death
The incomplete inactivation of Fgf8 in the limb ectoderm affects the morphogenesis of the anterior autopod through BMP-mediated cell death
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DOI：
10.1002/dvdy.21452
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发表时间：
2008-03-01
影响因子：
2.5
通讯作者：
Ros, Maria A.
中科院分区：
文献类型：
--
作者：
Delgado, Irene;Dominguez-Frutos, Elena;Ros, Maria A.
在这里，我们分析肢体发育后的条件失活FGF 8从上胚层，使用先前描述的MORE（Mox 2Cre）线。该细胞系驱动floxed Fgf 8等位基因的可变嵌合重组，导致小比例的AER细胞维持Fgf 8表达。Mox 2Cre的表型; Fgf 8肢与Msx 2Cre; Fgf 8前肢最相似，表明FGF 8的小但持久的表达相当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的Fgf 4上调，其缓冲了两种条件突变体之间Fgf 8表达模式的差异。Mox 2Cre; Fgf 8分支的分子分析显示，尽管Fgf 4上调，但它们在FGF信号传导减少的情况下发育。这些肢体还表现出异常的细胞死亡区域在前肢的前足，与异位域的Bmp 7表达，这可以解释异常的形态发生的前足重叠。.
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. .