Biglycan is a new extracellular component of the Chordin-BMP4 signaling pathway.
The BMP4 signaling pathway plays key roles during early embryonic development and for maintenance of adult homeostasis. In the extracellular space, BMP4 activity is regulated by a group of interacting molecules including the BMP antagonist Chordin, the metalloproteinase Tolloid and Twisted gastrulation (Tsg). In this study, we identified Biglycan (Bgn), a member of the small leucine-rich proteoglycan family, as a new extracellular modulator of BMP4 signaling. Xenopus Bgn (xBgn) is expressed uniformly in the ectoderm and mesoderm and their derivatives during development. Microinjection of Bgn mRNA induced secondary axes, dorsalized the mesoderm and inhibited BMP4 activity in Xenopus embryos. Biochemical experiments showed that Bgn binds BMP4 and Chordin, interaction that increased binding of BMP4 to Chordin. Bgn was also able to improve the efficiency of Chordin-Tsg complexes to block BMP4 activity. Using antisense morpholinos, we demonstrated that Bgn required Chordin to induce double axes in Xenopus. This work unveiled a new function for Bgn, its ability to regulate BMP4 signaling through modulation of Chordin anti-BMP4 activity.
Moreno
Mauricio
M
Department of Cell and Molecular Biology, Centre for Cell Regulation and Pathology, Millennium Nucleus in Developmental Biology, Faculty of Biological Sciences, P. Universidad Católica de Chile, Alameda, Santiago, Chile.
Muñoz
Rosana
R
Aroca
Francisco
F
Labarca
Mariana
M
Brandan
Enrique
E
Larraín
Juan
J
D000818:Animals; D058578:Biglycan; D019521:Body Patterning / Q000502:physiology; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism* / Q000502:physiology; D017931:DNA Primers; D004475:Ectoderm / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins / Q000378:metabolism* / Q000502:physiology; D047468:Immunoprecipitation; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000502:physiology; D008648:Mesoderm / Q000378:metabolism; D008845:Microinjections; D009841:Oligonucleotides; D011509:Proteoglycans / Q000378:metabolism* / Q000502:physiology; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D014981:Xenopus / Q000196:embryology*; D029867:Xenopus Proteins
D058578:Biglycan; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D009841:Oligonucleotides; D011509:Proteoglycans; D034741:RNA, Small Interfering; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus; C054234:chordin