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First published online October 23, 2009
doi: 10.1242/10.1242/dev.031534

Development 136, 3715-3728 (2009)
Published by The Company of Biologists 2009
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Review

The extracellular regulation of bone morphogenetic protein signaling

David Umulis1, Michael B. O'Connor2 and Seth S. Blair3,*

1 Department of Agricultural and Biological Engineering, and Weldon School of Biomedical Engineering, Bindley Bioscience Center, Purdue University, IN 47907, USA.
2 Department of Genetics, Cell Biology and Development, Howard Hughes Medical Institute, University of Minnesota, Minneapolis, MN 55455, USA.
3 Department of Zoology, University of Wisconsin, 250 North Mills Street, Madison, WI 53706, USA.

* Author for correspondence (ssblair{at}wisc.edu)

SUMMARY

In many cases, the level, positioning and timing of signaling through the bone morphogenetic protein (BMP) pathway are regulated by molecules that bind BMP ligands in the extracellular space. Whereas many BMP-binding proteins inhibit signaling by sequestering BMPs from their receptors, other BMP-binding proteins cause remarkably context-specific gains or losses in signaling. Here, we review recent findings and hypotheses on the complex mechanisms that lead to these effects, with data from developing systems, biochemical analyses and mathematical modeling.


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