Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, Los Angeles, United States.
USC Libraries Bioinformatics Services, University of Southern California, Los Angeles, Los Angeles, United States.
Elife. 2021 Jan 22;10:e62387. doi: 10.7554/eLife.62387.
Cranial neural crest (CNC) cells give rise to bone, cartilage, tendons, and ligaments of the vertebrate craniofacial musculoskeletal complex, as well as regulate mesoderm-derived craniofacial muscle development through cell-cell interactions. Using the mouse soft palate as a model, we performed an unbiased single-cell RNA-seq analysis to investigate the heterogeneity and lineage commitment of CNC derivatives during craniofacial muscle development. We show that Runx2, a known osteogenic regulator, is expressed in the CNC-derived perimysial and progenitor populations. Loss of in CNC-derivatives results in reduced expression of perimysial markers ( and ) as well as soft palate muscle defects in mice. We further reveal that Runx2 maintains perimysial marker expression through suppressing and that myogenesis is restored in mice. Collectively, our findings highlight the roles of Runx2, Twist1, and their interaction in regulating the fate of CNC-derived cells as they guide craniofacial muscle development through cell-cell interactions.
颅神经嵴（CNC）细胞产生脊椎动物颅面骨骼肌复合体的骨骼、软骨、肌腱和韧带，并通过细胞-细胞相互作用调节中胚层来源的颅面肌肉发育。我们使用小鼠软腭作为模型，通过无偏倚的单细胞 RNA-seq 分析来研究颅面肌肉发育过程中 CNC 衍生物的异质性和谱系决定。我们表明，已知的成骨调节因子 Runx2 在 CNC 衍生的肌周和祖细胞群体中表达。在 CNC 衍生物中缺失导致肌周标记物（和）的表达减少，以及 小鼠的软腭肌肉缺陷。我们进一步揭示，Runx2 通过抑制 维持肌周标记物的表达，并且在 小鼠中肌生成得到恢复。总之，我们的研究结果强调了 Runx2、Twist1 及其相互作用在调节 CNC 衍生细胞命运中的作用，因为它们通过细胞-细胞相互作用指导颅面肌肉发育。
