Ectodermal FGFs Induce Perinodular Inhibition of Limb Chondrogenesis in Vitro and in Vivo via FGF Receptor 2. Moftah, M., Z., Downie, S., A., Bronstein, N., B., Mezentseva, N., Pu, J., Maher, P., A., & Newman, S., A.
Paper abstract bibtex The formation of cartilage elements in the developing vertebrate limb, where they serve as primordia for the appendicular skeleton, is preceded by the appearance of discrete cellular condensations. Control of the size and spacing of these condensations is a key aspect of skeletal pattern formation. Limb bud cell cultures grown in the absence of ectoderm formed continuous sheet-like masses of cartilage. With the inclusion of ectoderm, these cultures produced one or more cartilage nodules surrounded by zones of noncartilaginous mesenchyme. Ectodermal fibroblast growth factors (FGF2 and FGF8), but not a mesodermal FGF (FGF7), substituted for ectoderm in inhibiting chondrogenic gene expression, with some combinations of the two ectodermal factors leading to well-spaced cartilage nodules of relatively uniform size. Treatment of cultures with SU5402, an inhibitor FGF receptor tyrosine kinase activity, rendered FGFs ineffective in inducing perinodular inhibition. Inhibition of production of FGF receptor 2 (FGFR2) by transfection of wing and leg cell cultures with antisense oligodeoxynucleotides blocked appearance of ectoderm-or FGF-induced zones of perinodular inhibition of chondrogenesis and, when introduced into the limb buds of developing embryos, led to shorter, thicker, and fused cartilage elements. Because FGFR2 is expressed mainly at sites of precartilage condensation during limb development in vivo and in vitro, these results suggest that activation of FGFR2 by FGFs during development elicits a lateral inhibitor of chondrogen-esis that limits the expansion of developing skeletal elements.
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title = {Ectodermal FGFs Induce Perinodular Inhibition of Limb Chondrogenesis in Vitro and in Vivo via FGF Receptor 2},
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notes = {Micromass paper, which concludes that FGFs act to inhibit chondrogeneis.<br>Important point: the assay is Alcian Blue staining after either 3 or 6 days of culture. This is therefore relevant to "late" <i><b>differentiation</b></i> questions, but not necessarily to early <i><b>patterning</b></i> questions. It contrasts with the results of Jelena in Supplementary Figure 32 of here paper. Her results suggested instead that FGF has an impact on <i><b>wavelength</b></i>.<br>},
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abstract = {The formation of cartilage elements in the developing vertebrate limb, where they serve as primordia for the appendicular skeleton, is preceded by the appearance of discrete cellular condensations. Control of the size and spacing of these condensations is a key aspect of skeletal pattern formation. Limb bud cell cultures grown in the absence of ectoderm formed continuous sheet-like masses of cartilage. With the inclusion of ectoderm, these cultures produced one or more cartilage nodules surrounded by zones of noncartilaginous mesenchyme. Ectodermal fibroblast growth factors (FGF2 and FGF8), but not a mesodermal FGF (FGF7), substituted for ectoderm in inhibiting chondrogenic gene expression, with some combinations of the two ectodermal factors leading to well-spaced cartilage nodules of relatively uniform size. Treatment of cultures with SU5402, an inhibitor FGF receptor tyrosine kinase activity, rendered FGFs ineffective in inducing perinodular inhibition. Inhibition of production of FGF receptor 2 (FGFR2) by transfection of wing and leg cell cultures with antisense oligodeoxynucleotides blocked appearance of ectoderm-or FGF-induced zones of perinodular inhibition of chondrogenesis and, when introduced into the limb buds of developing embryos, led to shorter, thicker, and fused cartilage elements. Because FGFR2 is expressed mainly at sites of precartilage condensation during limb development in vivo and in vitro, these results suggest that activation of FGFR2 by FGFs during development elicits a lateral inhibitor of chondrogen-esis that limits the expansion of developing skeletal elements.},
bibtype = {article},
author = {Moftah, Marie Z and Downie, Sherry A and Bronstein, Natalie B and Mezentseva, Nadezhda and Pu, Jiayu and Maher, Pamela A and Newman, Stuart A}
}
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