Mesoderm induction by BMP-4 and -7 heterodimers

Area of Science:

• Developmental Biology
• Molecular Biology
• Cell Signaling

Background:

• Bone morphogenetic proteins (BMPs) are TGF-beta superfamily growth factors vital during vertebrate embryogenesis.
• BMP-2, BMP-4, and BMP-7 are key ligands expressed in early embryonic development.
• Previous research indicated BMP-7 exhibits ventralizing activity but weak mesoderm induction as a homodimer.

Purpose of the Study:

• To investigate the mesoderm-inducing activity of BMP-7 homodimers and BMP-4/7 heterodimers.
• To determine if BMP-4/7 heterodimers exhibit potent activity at physiological concentrations.
• To provide evidence for the embryonic function of BMP-4/7 heterodimers.

Main Methods:

• Assessment of ventralizing activity in ectodermal explants and whole Xenopus embryos.
• Testing of purified recombinant BMP-4/7 heterodimers.
• Comparison of activity between homodimers and heterodimers at physiological concentrations.

Main Results:

• BMP-7 homodimer showed weak mesoderm-inducing activity, similar to BMP-2 and BMP-4.
• The purified recombinant Xenopus BMP-4/7 heterodimer demonstrated potent mesoderm-inducing activity.
• This potent activity was observed at physiological concentrations, unlike homodimers.

Conclusions:

• BMP-4/7 heterodimers, not homodimers, are potent inducers of mesoderm during vertebrate embryogenesis.
• The mesoderm-inducing activity of BMPs may not solely be an artifact of overexpression.
• This study provides the first evidence for an embryonic role of BMP-4/7 heterodimers.