Follistatin regulates bone morphogenetic protein-7 (BMP-7) activity to stimulate embryonic muscle growth.
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.
Amthor
Helge
H
Institute of Anatomy, University of Freiburg, Germany.
Christ
Bodo
B
Rashid-Doubell
Fiza
F
Kemp
C Fred
CF
Lang
Emily
E
Patel
Ketan
K
D028341:Activins / Q000502:physiology*; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000502:physiology; D005121:Extremities / Q000196:embryology / Q000502:physiology; D038681:Follistatin; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D009024:Morphogenesis / Q000502:physiology; D018482:Muscle, Skeletal / Q000196:embryology* / Q000502:physiology; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology; D016212:Transforming Growth Factor beta
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D038681:Follistatin; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D028341:Activins; C068686:Pax3 protein, mouse