Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. Signal., 15 September 2009
Vol. 2, Issue 88, p. ra55
[DOI: 10.1126/scisignal.2000304]

RESEARCH ARTICLES

Editor's Summary

Branch or Elongate
The graded distribution of morphogens, such as fibroblast growth factors (FGFs), is critically important for the patterning of tissues in the developing embryo. Binding of morphogens to heparan sulfate glycosaminoglycans (HSGAGs) controls their diffusion through the extracellular matrix (ECM); however, the extent to which these interactions modulate the activities of morphogens is unclear. Makarenkova et al. studied the differential effects of FGF7 and FGF10, two closely related FGFs with different biological activities, in the context of branching morphogenesis of epithelia from mouse embryonic lacrimal and submandibular glands. Whereas FGF7 induces branching of epithelial buds, FGF10 induces their elongation. Replacement of a single residue in the heparan-binding site of FGF10 with the corresponding residue of FGF7 resulted in a mutant FGF10 that acted as a functional mimic of FGF7; it diffused more readily into the ECM than did wild-type FGF10 and it induced branching rather than elongation of epithelial buds. Thus, not only are the gradients of morphogens established by their interactions with HSGAGs, but these interactions can also modulate their biological activities.

Citation: H. P. Makarenkova, M. P. Hoffman, A. Beenken, A. V. Eliseenkova, R. Meech, C. Tsau, V. N. Patel, R. A. Lang, M. Mohammadi, Differential Interactions of FGFs with Heparan Sulfate Control Gradient Formation and Branching Morphogenesis. Sci. Signal. 2, ra55 (2009).

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The control of branching morphogenesis.
D. Iber and D. Menshykau (2013)
Open Bio 3, 130088
   Abstract »    Full Text »    PDF »
Molecular Mechanisms of Fibroblast Growth Factor Signaling in Physiology and Pathology.
A. A. Belov and M. Mohammadi (2013)
Cold Spring Harb Perspect Biol 5, a015958
   Abstract »    Full Text »    PDF »
Morphogen transport.
P. Muller, K. W. Rogers, S. R. Yu, M. Brand, and A. F. Schier (2013)
Development 140, 1621-1638
   Abstract »    Full Text »    PDF »
Diversification of the Structural Determinants of Fibroblast Growth Factor-Heparin Interactions: IMPLICATIONS FOR BINDING SPECIFICITY.
R. Xu, A. Ori, T. R. Rudd, K. A. Uniewicz, Y. A. Ahmed, S. E. Guimond, M. A. Skidmore, G. Siligardi, E. A. Yates, and D. G. Fernig (2012)
J. Biol. Chem. 287, 40061-40073
   Abstract »    Full Text »    PDF »
Conversion of a Paracrine Fibroblast Growth Factor into an Endocrine Fibroblast Growth Factor.
R. Goetz, M. Ohnishi, S. Kir, H. Kurosu, L. Wang, J. Pastor, J. Ma, W. Gai, M. Kuro-o, M. S. Razzaque, et al. (2012)
J. Biol. Chem. 287, 29134-29146
   Abstract »    Full Text »    PDF »
Glycosaminoglycan-dependent restriction of FGF diffusion is necessary for lacrimal gland development.
X. Qu, Y. Pan, C. Carbe, A. Powers, K. Grobe, and X. Zhang (2012)
Development 139, 2730-2739
   Abstract »    Full Text »    PDF »
Klotho Coreceptors Inhibit Signaling by Paracrine Fibroblast Growth Factor 8 Subfamily Ligands.
R. Goetz, M. Ohnishi, X. Ding, H. Kurosu, L. Wang, J. Akiyoshi, J. Ma, W. Gai, Y. Sidis, N. Pitteloud, et al. (2012)
Mol. Cell. Biol. 32, 1944-1954
   Abstract »    Full Text »    PDF »
Extracellular Matrix in Development: Insights from Mechanisms Conserved between Invertebrates and Vertebrates.
N. H. Brown (2011)
Cold Spring Harb Perspect Biol 3, a005082
   Abstract »    Full Text »    PDF »
Barx2 and Fgf10 regulate ocular glands branching morphogenesis by controlling extracellular matrix remodeling.
C. Tsau, M. Ito, A. Gromova, M. P. Hoffman, R. Meech, and H. P. Makarenkova (2011)
Development 138, 3307-3317
   Abstract »    Full Text »    PDF »
Lacrimal Gland Development and Fgf10-Fgfr2b Signaling Are Controlled by 2-O- and 6-O-sulfated Heparan Sulfate.
X. Qu, C. Carbe, C. Tao, A. Powers, R. Lawrence, T. H. van Kuppevelt, W. V. Cardoso, K. Grobe, J. D. Esko, and X. Zhang (2011)
J. Biol. Chem. 286, 14435-14444
   Abstract »    Full Text »    PDF »
Influence of Heparin Mimetics on Assembly of the FGF{middle dot}FGFR4 Signaling Complex.
K. Saxena, U. Schieborr, O. Anderka, E. Duchardt-Ferner, B. Elshorst, S. L. Gande, J. Janzon, D. Kudlinzki, S. Sreeramulu, M. K. Dreyer, et al. (2010)
J. Biol. Chem. 285, 26628-26640
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882