FGF-4 and BMP-2 have opposite effects on limb growth.
Limb development is dependent on epithelial-mesenchymal interactions. The apical ectodermal ridge (AER), a specialized epithelium at the limb tip, stimulates proliferation of underlying mesenchyme, causing directed limb outgrowth (for review see ref. 2). Several genes are expressed in the mouse AER, including Fgf-4 (fibroblast growth factor-4) and Bmp-2 (bone morphogenetic protein-2), both of which encode secreted signalling molecules. Using a culture system developed to explore the function of molecules produced by the AER, we have shown that FGF-4 protein stimulates proliferation of mesenchyme in the early mouse limb-bud. This suggests that FGF-4 serves that major function of the AER. In contrast, BMP-2 inhibits limb growth, suggesting that as a result the AER may serve a hitherto unrecognized inhibitory function. Furthermore, the extent of limb outgrowth can be modulated by mixing the two signalling molecules, suggesting that limb growth is regulated by a combination of stimulatory and inhibitory signals from the AER.
Niswander
L
L
Department of Anatomy, School of Medicine, University of California, San Francisco 94143.
Martin
G R
GR
D000818:Animals; D019485:Bone Morphogenetic Proteins; D016895:Culture Media, Serum-Free; D046508:Culture Techniques; D005121:Extremities / Q000196:embryology*; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000502:physiology*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D006133:Growth Substances / Q000502:physiology; D051379:Mice; D011506:Proteins / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D015398:Signal Transduction
D019485:Bone Morphogenetic Proteins; D016895:Culture Media, Serum-Free; C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D006133:Growth Substances; D011506:Proteins; D011518:Proto-Oncogene Proteins; D005346:Fibroblast Growth Factors