TY - JOUR
T1 - wnt16 regulates spine and muscle morphogenesis through parallel signals from notochord and dermomyotome
AU - Watson, Claire J.
AU - Joyce Tang, W.
AU - Rojas, Maria F.
AU - Fiedler, Imke A.K.
AU - de Oca, Ernesto Morfin Montes
AU - Cronrath, Andrea R.
AU - Callies, Lulu K.
AU - Swearer, Avery Angell
AU - Ahmed, Ali R.
AU - Sethuraman, Visali
AU - Addish, Sumaya
AU - Farr, Gist H.
AU - Gómez, Arianna Ericka
AU - Rai, Jyoti
AU - Monstad-Rios, Adrian T.
AU - Gardiner, Edith M.
AU - Karasik, David
AU - Maves, Lisa
AU - Busse, Bjorn
AU - Hsu, Yi Hsiang
AU - Kwon, Ronald Young
N1 - 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.
PY - 2022/11/8
Y1 - 2022/11/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85142401312&partnerID=8YFLogxK
U2 - 10.1371/journal.pgen.1010496
DO - 10.1371/journal.pgen.1010496
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C2 - 36346812
AN - SCOPUS:85142401312
SN - 1553-7390
VL - 18
JO - PLoS Genetics
JF - PLoS Genetics
IS - 11
M1 - e1010496
ER -