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Effect of FGFR inhibitors on chicken limb development
Author(s) -
Horakova Dana,
Cela Petra,
Krejci Pavel,
Balek Lukas,
Moravcova Balkova Simona,
Matalova Eva,
Buchtova Marcela
Publication year - 2014
Publication title -
development, growth and differentiation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 66
eISSN - 1440-169X
pISSN - 0012-1592
DOI - 10.1111/dgd.12156
Subject(s) - fibroblast growth factor , fibroblast growth factor receptor , limb development , biology , limb bud , microbiology and biotechnology , apical ectodermal ridge , medicine , embryo , receptor , endocrinology , ectoderm , embryogenesis , biochemistry
Fibroblast growth factor ( FGF ) signalling appears essential for the regulation of limb development, but a full complexity of this regulation remains unclear. Here, we addressed the effect of three different chemical inhibitors of FGF receptor tyrosine kinases ( FGFR ) on growth and patterning of the chicken wings. The inhibitor PD 173074 caused shorter and thinner wing when using lower concentration. Microinjection of higher PD 173074 concentrations (25 and 50 mmol/L) into the wing bud at stage 20 resulted in the development of small wing rudiment or the total absence of the wing. Skeletal analysis revealed the absence of the radius but not ulna, deformation of metacarpal bones and/or a reduction of digits. Treatment with PD 161570 resembled the effects of PD 173074. NF 449 induced shortening and deformation of the developing wing with reduced autopodium. These malformed embryos mostly died at the stage HH 25–29. PD 173074 reduced chondrogenesis also in the limb micromass cultures together with early inhibition of cartilaginous nodule formation, evidenced by lack of sulphated proteoglycan and peanut agglutinin expression. The effect of FGFR inhibition on limb development observed here was unlikely mediated by excessive cell death as none of the inhibitors caused massive apoptosis at low concentrations. More probably, FGFR inhibition decreased both the proliferation and adhesion of mesenchymal chondroprogenitors. We conclude that FGFR signalling contributes to the regulation of the anterior‐posterior patterning of zeugopod during chicken limb development.