Activation of Fgf-4 and HoxD gene expression by BMP-2 expressing cells in the developing chick limb.
Bone morphogenetic protein-2 (BMP-2) has been implicated in the polarizing region signalling pathway, which specifies pattern across the antero-posterior of the developing vertebrate limb. Retinoic acid and Sonic Hedgehog (SHH) can act as polarizing signals; when applied anteriorly in the limb bud, they induce mirror-image digit duplications and ectopic Bmp-2 expression in anterior mesenchyme. In addition, the two signals can activate Fgf-4 expression in anterior ridge and HoxD expression in anterior mesenchyme. We tested the role of BMP-2 in this signalling cascade by ectopically expressing human BMP-2 (hBMP-2) at the anterior margin of the early wing bud using a replication defective retroviral vector, and found that ectopic expression of Fgf-4 was induced in the anterior part of the apical ectodermal ridge, followed later by ectopic expression of Hoxd-11 and Hoxd-13 in anterior mesenchyme. This suggests that BMP-2 is involved in regulating Fgf-4 and HoxD gene expression in the normal limb bud. Ectopically expressed hBMP-2 also induced duplication of digit 2 and bifurcation of digit 3, but could not produce the mirror-image digit duplications obtained with SHH-expressing cells. These results suggest that BMP-2 may be involved primarily in maintenance of the ridge, and in the link between patterning and outgrowth of the limb bud.
Duprez
D M
DM
Medical Molecular Biology Unit, Department of Molecular Pathology, University College London Medical School, UK.
Kostakopoulou
K
K
Francis-West
P H
PH
Tickle
C
C
Brickell
P M
PM
D000818:Animals; D019485:Bone Morphogenetic Proteins; D002460:Cell Line; D002642:Chick Embryo; D046508:Culture Techniques; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D018878:Limb Buds; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011784:Quail; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection; D014921:Wings, Animal / Q000196:embryology
D019485:Bone Morphogenetic Proteins; C496445:FGF4 protein, human; D051519:Fibroblast Growth Factor 4; C489493:HOXD11 protein, human; C513184:HOXD13 protein, human; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; C490939:Hoxd11 protein, mouse; D011506:Proteins; D011518:Proto-Oncogene Proteins; C509239:SHH protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D005346:Fibroblast Growth Factors