wnt16 regulates spine and muscle morphogenesis through parallel signals from notochord and dermomyotome
Standard
wnt16 regulates spine and muscle morphogenesis through parallel signals from notochord and dermomyotome. / Watson, Claire J; Tang, W Joyce; Rojas, Maria F; Fiedler, Imke A K; Morfin Montes de Oca, Ernesto; Cronrath, Andrea R; Callies, Lulu K; Swearer, Avery Angell; Ahmed, Ali R; Sethuraman, Visali; Addish, Sumaya; Farr, Gist H; Gómez, Arianna Ericka; Rai, Jyoti; Monstad-Rios, Adrian T; Gardiner, Edith M; Karasik, David; Maves, Lisa; Busse, Bjorn; Hsu, Yi-Hsiang; Kwon, Ronald Young.
In: PLOS GENET, Vol. 18, No. 11, e1010496, 11.2022.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - wnt16 regulates spine and muscle morphogenesis through parallel signals from notochord and dermomyotome
AU - Watson, Claire J
AU - Tang, W Joyce
AU - Rojas, Maria F
AU - Fiedler, Imke A K
AU - Morfin Montes de Oca, Ernesto
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 - 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
Y1 - 2022/11
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.
KW - Animals
KW - Notochord
KW - Zebrafish/genetics
KW - Spine
KW - Muscles
KW - Morphogenesis/genetics
KW - Larva
KW - Zebrafish Proteins/genetics
KW - Wnt Proteins/genetics
U2 - 10.1371/journal.pgen.1010496
DO - 10.1371/journal.pgen.1010496
M3 - SCORING: Journal article
C2 - 36346812
VL - 18
JO - PLOS GENET
JF - PLOS GENET
SN - 1553-7404
IS - 11
M1 - e1010496
ER -