wnt16 regulates spine and muscle morphogenesis through parallel signals from notochord and dermomyotome

Claire J. Watson, W. Joyce Tang, Maria F. Rojas, Imke A.K. Fiedler, Ernesto Morfin Montes de Oca, Andrea R. Cronrath, Lulu K. Callies, Avery Angell Swearer, Ali R. Ahmed, Visali Sethuraman, Sumaya Addish, Gist H. Farr, Arianna Ericka Gómez, Jyoti Rai, Adrian T. Monstad-Rios, Edith M. Gardiner, David Karasik, Lisa Maves, Bjorn Busse, Yi Hsiang HsuRonald Young Kwon

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Bone and muscle are coupled through developmental, mechanical, paracrine, and autocrine signals. Genetic variants at the CPED1-WNT16 locus are dually associated with bone- and muscle-related traits. While Wnt16 is necessary for bone mass and strength, this fails to explain pleiotropy at this locus. Here, we show wnt16 is required for spine and muscle morphogenesis in zebrafish. In embryos, wnt16 is expressed in dermomyotome and developing notochord, and contributes to larval myotome morphology and notochord elongation. Later, wnt16 is expressed at the ventral midline of the notochord sheath, and contributes to spine mineralization and osteoblast recruitment. Morphological changes in wnt16 mutant larvae are mirrored in adults, indicating that wnt16 impacts bone and muscle morphology throughout the lifespan. Finally, we show that wnt16 is a gene of major effect on lean mass at the CPED1-WNT16 locus. Our findings indicate that Wnt16 is secreted in structures adjacent to developing bone (notochord) and muscle (dermomyotome) where it affects the morphogenesis of each tissue, thereby rendering wnt16 expression into dual effects on bone and muscle morphology. This work expands our understanding of wnt16 in musculoskeletal development and supports the potential for variants to act through WNT16 to influence bone and muscle via parallel morphogenetic processes.

Original languageEnglish
Article numbere1010496
JournalPLoS Genetics
Issue number11
StatePublished - 8 Nov 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright: © 2022 Watson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Dive into the research topics of 'wnt16 regulates spine and muscle morphogenesis through parallel signals from notochord and dermomyotome'. Together they form a unique fingerprint.

Cite this