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First published online April 22, 2004
doi: 10.1242/10.1242/dev.01045

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Connective-tissue growth factor modulates WNT signalling and interacts with the WNT receptor complex

Sara Mercurio^1,*, Branko Latinkic^1,, Nobue Itasaki², Robb Krumlauf^2, and J. C. Smith^1,*,

¹ Division of Developmental Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
² Division of Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK

Author for correspondence (e-mail: jim{at}welc.cam.ac.uk)

Accepted 17 December 2003

Connective-tissue growth factor (CTGF) is a member of the CCN family of secreted proteins. CCN family members contain four characteristic domains and exhibit multiple activities: they associate with the extracellular matrix, they can mediate cell adhesion, cell migration and chemotaxis, and they can modulate the activities of peptide growth factors. Many of the effects of CTGF are thought to be mediated by binding to integrins, whereas others may be because of its recently identified ability to interact with BMP4 and TGFß. We demonstrate, using Xenopus embryos, that CTGF also regulates signalling through the Wnt pathway, in accord with its ability to bind to the Wnt co-receptor LDL receptor-related protein 6 (LRP6). This interaction is likely to occur through the C-terminal (CT) domain of CTGF, which is distinct from the BMP- and TGFß-interacting domain. Our results define new activities of CTGF and add to the variety of routes through which cells regulate growth factor activity in development, disease and tissue homeostasis.

Key words: Xenopus, CTGF, CCN family, Wnt signalling, LRP6

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