Purification and Molecular Cloning of a Novel Group of Bmps and Localization of Bmp Mrna in Developing Bone

Abstract

Using a novel purification scheme, we have characterized BMP as a 30kD fraction. After reduction, which destroys biological activity, this fraction was shown to be comprised of individual polypeptides with molecular weights of 30kD, 18kD and 16kD. Molecular cloning of these polypeptides resulted in the identification of 4 previously undescribed genes (BMP-1, BMP-2A, BMP-2B, and BMP-3) each of which is capable of directing de novo cartilage formation in vivo. While BMP-1 appears to be unrelated to other known growth factors, the derived amino acid sequence of BMP-2A, 2B, and 3 indicate that they are new members of the TGFb gene family. BMP-1, 2A and 2B are expressed in rat embryos during morphogenesis and can be localized by in situ hybridization to developing limb buds. BMP-3 localizes to neural ectoderm and later on in development to newly forming periosteum. Comparisons to other members of the TGFb family suggest that these newly identified BMPs are involved in pattern formation during early skeletal development.