Developing control of the heart

Developing control of the heart

28 August 2008
Molecular biologists working at an American and several Japanese research institutions have unmasked an important regulator of embryonic development of the heart. The compound, an insulin-like growth-factor-binding protein (IGFBP), inhibits the standard Wnt signaling pathway that plays a key role in the initiation, growth and development of the heart. Abnormalities of formation of the heart — the first embryonic organ to form — are the most common congenital birth defects in humans.

The researchers recently reported in Nature1 that the compound IGFBP-4 could stimulate generation of cardiomyocytes, the cells from which heart muscle tissue is produced. Although IGFBPs are typically characterized by their ability to bind and modulate the action of insulin-like growth factors (IGFs), the researchers were able to show experimentally that in this case, the activity of IGFBP-4 involved no binding of IGFs. In fact, IGFBP-4 appears to inhibit Wnt signaling by interacting with a Wnt receptor and co-receptor to prevent them from binding Wnt. At different times of the process Wnt signaling can stimulate or repress development of the heart.

The researchers suggest that IGFBP-4 can regulate development via inhibiting Wnt signaling, and that IGFs can also play a modulation role through binding and sequestering IGFBP-4.
Reference

1. Zhu, W.,1,8 Shiojima, I.,1,8 Ito, Y.,2,8 Li, Z.,1 Ikeda, H.,1 Yoshida, M.,1 Naito, A.T.,1 Nishi, J.,1 Ueno, H.,3 Umezawa, A.,4 Minamino, T.,1 Nagai, T.,1 Kikuchi, A.,5 Asashima, M.2,6,7,9 & Komuro, I.1 IGFBP-4 is an inhibitor of canonical Wnt signaling required for cardiogenesis. Nature 454, 345–350 (2008). article

Authors and Affiliations
1Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
2ICORP Organ Regeneration Project, Japan Science and Technology Agency (JST), Tokyo 153-8902, Japan
3Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA
4Department of Reproductive Biology, National Institute for Child Health and Development, Tokyo 157-8535, Japan
5Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan
6Department of Life Sciences (Biology), Graduate School of Arts and Science, The University of Tokyo, Tokyo 153-8902, Japan
7National Institute of Advanced Industrial Sciences and Technology (AIST), Ibaraki 305-8562, Japan
8These authors contributed equally to this work.
9 Makoto Asashima is a member of A-IMBN.

Source: http://www.natureasia.com/A-IMBN/article.php?id=135