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

Autor: Watson CJ; Department of Orthopaedics and Sports Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.; Insitute for Stem Cell and Regenerative Medicines, University of Washington, Seattle Washington, United States of America., Tang WJ; Department of Orthopaedics and Sports Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.; Insitute for Stem Cell and Regenerative Medicines, University of Washington, Seattle Washington, United States of America., Rojas MF; Department of Orthopaedics and Sports Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.; Insitute for Stem Cell and Regenerative Medicines, University of Washington, Seattle Washington, United States of America., Fiedler IAK; Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Morfin Montes de Oca E; Department of Orthopaedics and Sports Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.; Insitute for Stem Cell and Regenerative Medicines, University of Washington, Seattle Washington, United States of America., Cronrath AR; Department of Orthopaedics and Sports Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.; Insitute for Stem Cell and Regenerative Medicines, University of Washington, Seattle Washington, United States of America., Callies LK; Department of Orthopaedics and Sports Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.; Insitute for Stem Cell and Regenerative Medicines, University of Washington, Seattle Washington, United States of America., Swearer AA; Department of Orthopaedics and Sports Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.; Insitute for Stem Cell and Regenerative Medicines, University of Washington, Seattle Washington, United States of America., Ahmed AR; Department of Orthopaedics and Sports Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.; Insitute for Stem Cell and Regenerative Medicines, University of Washington, Seattle Washington, United States of America., Sethuraman V; Department of Orthopaedics and Sports Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.; Insitute for Stem Cell and Regenerative Medicines, University of Washington, Seattle Washington, United States of America., Addish S; Department of Orthopaedics and Sports Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.; Insitute for Stem Cell and Regenerative Medicines, University of Washington, Seattle Washington, United States of America., Farr GH 3rd; Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, Washington, United States of America., Gómez AE; Department of Orthopaedics and Sports Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.; Insitute for Stem Cell and Regenerative Medicines, University of Washington, Seattle Washington, United States of America., Rai J; Department of Orthopaedics and Sports Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.; Insitute for Stem Cell and Regenerative Medicines, University of Washington, Seattle Washington, United States of America., Monstad-Rios AT; Department of Orthopaedics and Sports Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.; Insitute for Stem Cell and Regenerative Medicines, University of Washington, Seattle Washington, United States of America., Gardiner EM; Department of Orthopaedics and Sports Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.; Insitute for Stem Cell and Regenerative Medicines, University of Washington, Seattle Washington, United States of America., Karasik D; Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts, United States of America., Maves L; Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, Washington, United States of America.; Department of Pediatrics, Division of Cardiology, University of Washington School of Medicine, Seattle, Washington, United States of America., Busse B; Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Hsu YH; Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts, United States of America.; Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.; Broad Institute of Harvard and Massachusetts Institute of Technology, Boston, Massachusetts, United States of America., Kwon RY; Department of Orthopaedics and Sports Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.; Insitute for Stem Cell and Regenerative Medicines, University of Washington, Seattle Washington, United States of America.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2022 Nov 08; Vol. 18 (11), pp. e1010496. Date of Electronic Publication: 2022 Nov 08 (Print Publication: 2022).
DOI: 10.1371/journal.pgen.1010496
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
(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.)
Databáze: MEDLINE
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