Editors' ChoiceMorphogens

Defining the Limit

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Science's STKE  12 Feb 2002:
Vol. 2002, Issue 119, pp. tw72
DOI: 10.1126/stke.2002.119.tw72

Bone morphogenic proteins (BMPs) are morphogens of the transforming growth factor-β superfamily that act during development to control pattern formation. Some BMPs, specifically BMP-2 and BMP-4, exhibit signaling over a short range, whereas other BMPs are more diffusible and exhibit longer range signaling. Ohkawara et al. identified a conserved sequence of basic amino acids in the NH2-terminus of BMP-4 that is not present in the more diffusible members of the family. They tested the wild-type and mutants of BMP-2 and BMP-4 in those conserved basic residues and found that deletion or point mutation resulted in a more diffusible signal in Xenopus animal cap assays that allow the response to morphogens to be monitored by activation of gene expression or morphogenic changes. BMP-4 interacted with heparin conjugated to beads and required heparan sulfate proteoglycans (HSPGs) on the surface of animal caps in order to bind to the caps. The ability to bind to heparin was severely limited by deletion of the basic residues. Thus, Ohkawara et al. have defined an HSPG-binding motif that may be one mechanism by which morphogenic signaling is spatially limited.

B. Ohkawara, S.-i. Iemura, P. ten Dijke, N. Ueno, Action range of BMP is defined by its N-terminal basic amino acid core. Curr. Biol. 12, 205-209 (2002). [Online Journal]

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