Fine tuning of growth factor signals depends on fibrillin microfibril networks
Article first published online: 25 MAR 2004
Copyright © 2004 Wiley-Liss, Inc.
Birth Defects Research Part C: Embryo Today: Reviews
Volume 72, Issue 1, pages 37–50, March 2004
How to Cite
Charbonneau, N. L., Ono, R. N., Corson, G. M., Keene, D. R. and Sakai, L. Y. (2004), Fine tuning of growth factor signals depends on fibrillin microfibril networks. Birth Defects Research Part C: Embryo Today: Reviews, 72: 37–50. doi: 10.1002/bdrc.20000
- Issue published online: 25 MAR 2004
- Article first published online: 25 MAR 2004
- National Institutes of Health. Grant Number: AR46811
- Shriners Hospitals for Children
- Scleroderma Foundation
- National Marfan Foundation
- TGF beta;
- marfan syndrome
Growth factors, potent regulators of cell differentiation, tissue morphogenesis, tissue homeostasis, and cellular response to injury, reside in the extracellular matrix. Genetic evidence in humans and mice as well as biochemical data implicate fibrillins and LTBPs in the extracellular control of TGFβ and BMP signaling. Fibrillins and LTBPs form tissue-specific and temporally regulated microfibril networks. In the developing embryo, three fibrillins and four LTBPs contribute molecular heterogeneity to microfibril networks, and provide different templates upon which TGFβ-related growth factors can be positioned. By accommodating this molecular heterogeneity, microfibril architecture can orchestrate a variety of different signals in very specific tissue locations. Human fibrillinopathies display a broad phenotypic spectrum from tall to short stature, from hypermobile joints to joint contractures and stiffness, and from severe to mild or no cardiovascular manifestations. A spectrum of growth factor dysregulation may be caused by differential effects of mutations in fibrillins on microfibril architecture, thus altering appropriate targeting or positioning of growth factors within microfibril networks. Growth factor dysregulation may help to explain the broad phenotypic spectrum of the fibrillinopathies. Birth Defects Research (Part C) 72:37–50, 2004. © 2004 Wiley-Liss, Inc.