The incomplete inactivation of Fgf8 in the limb ectoderm affects the morphogenesis of the anterior autopod through BMP-mediated cell death.
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.
Delgado
Irene
I
Departamento de Anatomía y Biología Celular, Universidad de Cantabria, C/Herrera Oria s/n, E-39011 Santander, Spain.
Domínguez-Frutos
Elena
E
Schimmang
Thomas
T
Ros
Maria A
MA
D000818:Animals; D019521:Body Patterning; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D016923:Cell Death; D004475:Ectoderm / Q000196:embryology / Q000502:physiology; D005121:Extremities / Q000196:embryology*; D051519:Fibroblast Growth Factor 4 / Q000378:metabolism; D051524:Fibroblast Growth Factor 8 / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D018878:Limb Buds / Q000196:embryology*; D051379:Mice; D008817:Mice, Mutant Strains; D009024:Morphogenesis; D015398:Signal Transduction
D019485:Bone Morphogenetic Proteins; C496446:Fgf4 protein, mouse; C496457:Fgf8 protein, mouse; D051519:Fibroblast Growth Factor 4; D051524:Fibroblast Growth Factor 8