Wnt16 通过来自脊索和真皮肌节的平行信号调节脊柱和肌肉的形态发生。
wnt16 regulates spine and muscle morphogenesis through parallel signals from notochord and dermomyotome.
机构信息
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.
出版信息
PLoS Genet. 2022 Nov 8;18(11):e1010496. doi: 10.1371/journal.pgen.1010496. eCollection 2022 Nov.
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.
骨骼和肌肉通过发育、机械、旁分泌和自分泌信号相互关联。CPED1-WNT16 基因座的遗传变异与骨骼和肌肉相关特征双重相关。虽然 Wnt16 对于骨量和骨强度是必需的,但这并不能解释该基因座的表型多样性。在这里,我们展示了 wnt16 在斑马鱼的脊柱和肌肉发生中是必需的。在胚胎中,wnt16 在真皮肌和发育中的脊索中表达,并有助于幼虫肌节形态和脊索伸长。后来,wnt16 在脊索鞘的腹中线表达,并有助于脊柱矿化和成骨细胞募集。wnt16 突变体幼虫的形态变化在成年期得到了反映,表明 wnt16 影响整个生命周期的骨骼和肌肉形态。最后,我们表明 wnt16 是 CPED1-WNT16 基因座上瘦体重的主要效应基因。我们的研究结果表明,Wnt16 是在发育中的骨骼(脊索)和肌肉(真皮肌)相邻结构中分泌的,它影响每个组织的形态发生,从而使 wnt16 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 Wnt16 在肌肉骨骼发育中的理解,并支持了通过平行形态发生过程,通过 WNT16 影响骨骼和肌肉的变异的潜在可能性。