wnt16 regulates spine and muscle morphogenesis through parallel signals from notochord and dermomyotome.
wnt16 regulates spine and muscle morphogenesis through parallel signals from notochord and dermomyotome.
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DOI：
10.1371/journal.pgen.1010496
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发表时间：
2022-11
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影响因子：
4.5
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中科院分区：
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骨骼和肌肉通过发育、机械、旁分泌和自分泌信号耦合。CPED 1-WNT 16基因座的遗传变异与骨骼和肌肉相关性状双重相关。虽然Wnt 16是骨量和强度所必需的，但这无法解释该位点的多效性。在这里，我们发现wnt 16是斑马鱼脊椎和肌肉形态发生所必需的。在胚胎中，wnt 16在表皮肌节和发育中的脊索中表达，并对幼虫肌节形态和脊索伸长有贡献。随后，wnt 16在脊索鞘的腹侧中线表达，并有助于脊柱矿化和成骨细胞的募集。wnt 16突变体幼虫的形态变化在成虫中也有反映，表明wnt 16在整个生命周期中影响骨骼和肌肉形态。最后，我们表明，wnt 16是一个基因的主要影响瘦肉质量在CPED 1-WNT 16位点。我们的研究结果表明，Wnt 16分泌在邻近发育中的骨骼（脊索）和肌肉（皮肌节）的结构中，它影响每个组织的形态发生，从而使Wnt 16表达对骨骼和肌肉形态产生双重影响。这项工作扩展了我们对WNT 16在肌肉骨骼发育中的理解，并支持变体通过WNT 16通过平行的形态发生过程影响骨骼和肌肉的潜力。在人类中，遗传变异（个体之间不同的DNA序列）已被确定，似乎影响两种组织，骨骼和骨骼肌。然而，单基因和遗传变异如何对这两种组织产生双重影响还不清楚。在这项研究中，我们发现wnt 16基因在斑马鱼发育过程中对肌肉和骨骼的大小和形状的指定是必需的。我们还解开了Wnt 16如何影响这两种组织：邻近肌肉和骨骼的不同细胞群分泌Wnt 16，在那里它作为指导每个组织大小和形状的信号。这一点很重要，因为在人类中，WNT 16基因附近的遗传变异对骨骼和肌肉相关性状都有影响。这项研究扩展了我们对WNT 16在骨骼和肌肉发育中作用的理解，并有助于解释WNT 16附近的遗传变异如何影响这两种组织的性状。此外，WNT 16正在积极探索作为骨质疏松症治疗的靶点，因此我们的研究可能对靶向WNT 16同时治疗骨骼和肌肉的潜力产生影响。
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. In humans, genetic variants (DNA sequences that vary amongst individuals) have been identified that appear to influence two tissues, bone and skeletal muscle. However, how single genes and genetic variants exert dual influence on both tissues is not well understood. In this study, we found that the wnt16 gene is necessary for specifying the size and shape of both muscle and bone during development in zebrafish. We also disentangled how wnt16 affects both tissues: distinct cellular populations adjacent to muscle and bone secrete Wnt16, where it acts as a signal guiding the size and shape of each tissue. This is important because in humans, genetic variants near the WNT16 gene have effects on both bone- and muscle-related traits. This study expands our understanding of the role of WNT16 in bone and muscle development, and helps to explain how genetic variants near WNT16 affect traits for both tissues. Moreover, WNT16 is actively being explored as a target for osteoporosis therapies, thus our study could have implications with regard to the potential of targeting WNT16 to treat bone and muscle simultaneously.
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影响因子：
1.5
作者：
DeLaurier, April;Eames, B. Frank;Blanco-Sanchez, Bernardo;Peng, Gang;He, Xinjun;Swartz, Mary E.;Ullmann, Bonnie;Westerfield, Monte;Kimmel, Charles B.
通讯作者：
Kimmel, Charles B.
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
4.8
作者：
Alam, Imranul;Alkhouli, Mohammed;Econs, Michael J.
通讯作者：
Econs, Michael J.
影响因子：
4.6
作者：
Caetano-Lopes, Joana;Henke, Katrin;Harris, Matthew P.
通讯作者：
Harris, Matthew P.
影响因子：
16.8
作者：
Daane, Jacob M.;Dornburg, Alex;Harris, Matthew P.
通讯作者：
Harris, Matthew P.