Interaction between the signaling molecules WNT7a and SHH during vertebrate limb development: dorsal signals regulate anteroposterior patterning.
Growth and patterning of the vertebrate limb are controlled by the ridge, posterior mesenchyme, and non-ridge ectoderm. Fibroblast growth factor 4 (FGF4) and Sonic hedgehog (SHH) can mediate signaling from the ridge and posterior mesenchyme, respectively. Here we show that dorsal ectoderm is required together with FGF4 to maintain Shh expression. Removal of dorsal ectoderm results in loss of posterior skeletal elements, which can be rescued by exogenous SHH. Wnt7a, which is expressed in dorsal ectoderm, provides the signal required for Shh expression and formation of posterior structures. These results provide evidence that all three axes (dorsoventral, proximodistal, and anteroposterior) are intimately linked by the respective signals WNT7a, FGF4, and SHH during limb out-growth and patterning.
Yang
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Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Niswander
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D000818:Animals; D030161:Avian Proteins; D001483:Base Sequence; D002642:Chick Embryo; D017931:DNA Primers; D004475:Ectoderm / Q000502:physiology; D004627:Embryonic Induction; D005314:Embryonic and Fetal Development; D005121:Extremities / Q000196:embryology; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D053823:Hedgehog Proteins; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators; D051153:Wnt Proteins
D030161:Avian Proteins; D017931:DNA Primers; C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D053823:Hedgehog Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; C490509:WNT7A protein, Gallus gallus; D051153:Wnt Proteins; C490508:Wnt7a protein, mouse; D005346:Fibroblast Growth Factors