Bone morphogenetic protein signaling: the pathway and its regulation

Abstract

In the mid-1960s, bone morphogenetic proteins (BMPs) were first identified in the extracts of bone to have the remarkable ability to induce heterotopic bone. When the Drosophila gene decapentaplegic (dpp) was first identified to share sequence similarity with mammalian BMP2/BMP4 in the late-1980s, it became clear that secreted BMP ligands can mediate processes other than bone formation. Following this discovery, collaborative efforts between Drosophila geneticists and mammalian biochemists made use of the strengths of their respective model systems to identify BMP signaling components and delineate the pathway. The ability to conduct genetic modifier screens in Drosophila with relative ease was critical in identifying the intracellular signal transducers for BMP signaling and the related transforming growth factor-beta/activin signaling pathway. Such screens also revealed a host of genes that encode other core signaling components and regulators of the pathway. In this review, we provide a historical account of this exciting time of gene discovery and discuss how the field has advanced over the past 30 years. We have learned that while the core BMP pathway is quite simple, composed of 3 components (ligand, receptor, and signal transducer), behind the versatility of this pathway lies multiple layers of regulation that ensures precise tissue-specific signaling output. We provide a sampling of these discoveries and highlight many questions that remain to be answered to fully understand the complexity of BMP signaling.

Postsynaptic BMP signaling regulates myonuclear properties inDrosophilalarval muscles

“…Punt KD in muscles resulted in a robust reduction in size and DNA content (less 64C, more 32C ploidy); however, the effects on DNA content were stronger in synaptic than non-synaptic nuclei. Punt is believed to be the only BMP type II receptor expressed in larval muscle (Akiyama et al, 2024), where it functions to stabilize ligand binding and phosphorylate the type I receptor for activation. However, Punt also associates with Activin receptors (Babo), and like BMP, this other TGF-β pathway has been shown to influence NMJ size and activity (Ellis et al, 2010; Fuentes-Medel et al, 2012; Kim and O’Connor, 2014).…”

Editorial: Tissue regeneration using dental stem cells

“…The bone morphogenetic proteins (BMPs) are recognised as among the most important players in many processes related to the formation and maintenance of various tissues, including bone, cartilage, and muscle (Akiyama et al, 2023). In addition, BMPs hold significant potential as bioactive factors for tooth root regeneration for regulating signalling pathways in various stages of tooth root development.…”