BMP-2/-4 mediate programmed cell death in chicken limb buds

• Published in: Development (Cambridge) Vol. 122; no. 12; pp. 3725 - 3734
• Main Authors: Yokouchi, Y, Sakiyama, J, Kameda, T, Iba, H, Suzuki, A, Ueno, N, Kuroiwa, A
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Limited 01-12-1996
• Subjects: Animals; Apoptosis; Bone and Bones - embryology; Bone Morphogenetic Protein 2; Bone Morphogenetic Protein 4; Bone Morphogenetic Protein Receptors; Bone Morphogenetic Proteins - metabolism; Chick Embryo; Ducks - embryology; Gene Transfer Techniques; Limb Buds - embryology; Mesoderm - pathology; Necrosis; Receptors, Cell Surface - genetics; Receptors, Growth Factor; Signal Transduction; Species Specificity; Transforming Growth Factor beta - metabolism
• ISSN: 0950-1991; 1477-9129
• DOI: 10.1242/dev.122.12.3725

During limb development, the mesenchymal cells in restricted areas of limb bud, anterior necrotic zone, posterior necrotic zone, opaque zone and interdigital necrotic zones, are eliminated by programmed cell death. The transcripts of bone morphogenetic protein (Bmp)-2 and −4 were first detected in the areas where cell death was observed, then showed overlapping expression with the programmed cell death zones except the opaque zone. To investigate the function of BMP-2 and BMP-4 during limb pattern formation, the dominant negative form of BMP receptor was overexpressed in chick leg bud via a replication-competent retrovirus to block the endogenous BMP-2/-4 signaling pathway. This resulted in excess web formation at the anterior and posterior regions of limb buds in addition to marked suppression of the regression of webbing at the interdigital regions. Significant reductions in the number of apoptotic cells in these three necrotic zones were found in the limb buds which received the virus carrying dominant negative BMP receptor. This indicates that extra tissue formation is due to suppression of programmed cell death in the three necrotic zones. Moreover, BMP-2/-4 protein induced apoptosis of mesenchymal cells isolated from the interdigital region in vitro. Other TGFbeta family proteins as TGFbeta1 and Activin did not show this effect. These results suggest that BMP-2 and BMP-4 are the apoptotic signal molecules of the programmed cell death process in the chick limb buds.