Direct binding of follistatin to a complex of bone-morphogenetic protein and its receptor inhibits ventral and epidermal cell fates in early Xenopus embryo

Direct binding of follistatin to a complex of bone-morphogenetic protein and its receptor inhibits ventral and epidermal cell fates in early Xenopus embryo

^* Department of Developmental Biology, National Institute for Basic Biology, 38 Nishigonaka, Myodaiji, Okazaki, 444-8585 Japan; ^†Department of Biology, Yokohama City University, 22-2 Seto, Kanazawa-ku Yokohama, 236-0027 Japan; ^‡Mikoshiba Calciosignal Net Project, Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology Corporation 2-9-3 Shimomeguro, Meguro-ku, Tokyo, 153-0064 Japan; ^§Department of Reproductive Medicine, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0633; ^¶The Institute for Enzyme Research, The University of Tokushima, 3-18-15 Kuramoto, Tokushima, 770-8503 Japan; and ^‖Department of Molecular Biomechamics, School of Life Science, Graduate University for Advanced Studies, 38 Nishigonaka, Myodaiji, Okazaki, 444-8585 Japan

Edited by Igor B. Dawid, National Institute of Child Health and Human Development, Bethesda, MD, and approved May 19, 1998 (received for review December 30, 1997)

Abstract

In early development of Xenopus laevis, it is known that activities of polypeptide growth factors are negatively regulated by their binding proteins. In this study, follistatin, originally known as an activin-binding protein, was shown to inhibit all aspects of bone morphogenetic protein (BMP) activity in early Xenopus embryos. Furthermore, using a surface plasmon resonance biosensor, we demonstrated that follistatin can directly interact with multiple BMPs at significantly high affinities. Interestingly, follistatin was found to be noncompetitive with the BMP receptor for ligand binding and to form a trimeric complex with BMP and its receptor. The results suggest that follistatin acts as an organizer factor in early amphibian embryogenesis by inhibiting BMP activities by a different mechanism from that used by chordin and noggin.

Footnotes

↵ ‡‡ To whom correspondence should be addressed. e-mail: nueno{at}nibb.ac.jp.
This paper was submitted directly (Track II) to the Proceedings Office.
ABBREVIATIONS:

BMP,

bone morphogenetic protein;

FS-288,

follistatin-288;

TGF-β,

transforming growth factor-β;

sBMPR,

soluble form of BMP type IA receptor;

RT,

reverse transcription;

2D,

two-dimensional