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Wnt signalling controls the response to mechanical loading during zebrafish joint development

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)2798-2809
Number of pages12
JournalDevelopment (Cambridge)
Volume144
Issue number15
DOIs
DateAccepted/In press - 14 Jun 2017
DatePublished (current) - 1 Aug 2017

Abstract

Joint morphogenesis requires mechanical activity during development. Loss of mechanical strain causes abnormal joint development, which can impact long-term joint health. Although cell orientation and proliferation are known to shape the joint, dynamic imaging of developing joints in vivo has not been possible in other species. Using genetic labelling techniques in zebrafish we were able, for the first time, to dynamically track cell behaviours in intact moving joints. We identify that proliferation and migration, which contribute to joint morphogenesis, are mechanically controlled and are significantly reduced in immobilised larvae. By comparison with strain maps of the developing skeleton, we identify canonical Wnt signalling as a candidate for transducing mechanical forces into joint cell behaviours. We show that, in the jaw, Wnt signalling is reduced specifically in regions of high strain in response to loss of muscle activity. By pharmacological manipulation of canonical Wnt signalling, we demonstrate that Wnt acts downstream of mechanical activity and is required for joint patterning and chondrocyte maturation. Wnt16, which is also downstream of muscle activity, controls proliferation and migration, but plays no role in chondrocyte intercalation.

    Research areas

  • Cartilage, Joint, Mechanics, Morphogenesis, Wnt, Zebrafish

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via The Comp[any of Biologists at https://doi.org/10.1242/dev.153528 . Please refer to any applicable terms of use of the publisher.

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    Licence: CC BY

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