Follistatin Regulates Bone Morphogenetic Protein-7 (BMP-7) Activity to Stimulate Embryonic Muscle Growth

• Published in: Developmental biology 2002-03, Vol.243 (1), p.115-127
• Main Authors: Amthor, Helge, Christ, Bodo, Rashid-Doubell, Fiza, Kemp, C.Fred, Lang, Emily, Patel, Ketan
• Format: Article
• Language: English
• Subjects: Activins - physiology; Animals; Biacore; BMP; Bone Morphogenetic Protein 2; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins - physiology; Chick Embryo; DNA-Binding Proteins - physiology; embryo; Embryo, Nonmammalian - physiology; Extremities - embryology; Extremities - physiology; Follistatin; Gene Expression Regulation, Developmental - physiology; Morphogenesis - physiology; muscle development; Muscle, Skeletal - embryology; Muscle, Skeletal - physiology; MyoD; Noggin; Paired Box Transcription Factors; Pax-3; PAX3 Transcription Factor; Signal Transduction; Transcription Factors - physiology; Transforming Growth Factor beta
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1006/dbio.2001.0555

Bone morphogenetic proteins (BMPs) can either promote growth of embryonic muscle by expanding the Pax-3-expressing muscle precursor population or restrict its development by inducing apoptosis. Follistatin, a proposed BMP antagonist, is expressed in embryonic muscle. Deficiency in Follistatin results in muscle defects and postnatal asphyxia. Here, we report that during chick limb development Follistatin enhances BMP-7 action to induce muscle growth but prevents the ability of BMP-7 to induce apoptosis and muscle loss. Follistatin, unlike another BMP-binding protein, Noggin, promotes Pax-3 expression and transiently delays muscle differentiation and thus exerts proliferative signalling during muscle development. We provide data which show that Follistatin binds BMP-7 and BMP-2 at low affinities and that the binding is reversible. These data suggest that Follistatin acts to present BMPs to myogenic cells at a concentration that permits stimulation of embryonic muscle growth.