Tongue muscles are derived from mesodermal cells, while signals driven by cranial neural crest cells (CNCCs) regulate tongue myogenesis via tissue–tissue interaction. Based on such mechanisms of interaction, congenital tongue defects occur in CNC-related syndromes in humans. This study utilized a pathologic model for the syndrome of congenital bony syngnathia, Wnt1-Cre;pMes-Bmp4 mouse line, to explore impacts of enhanced CNCCs-originated BMP4 signal on tongue myogenesis via tissue-tissue interaction. Our results revealed that microglossia, a clinical phenotype of congenital bony syngnathia in humans exhibited in Wnt1-Cre;pMes-Bmp4 mice due to impaired myogenesis. The augmented BMP4 signal affected the distal distribution, proliferation, and differentiation of myogenic cells as well as tendon patterning, resulting in disarrangement and atrophy of tongue muscles and the loss of the anterior digastric muscle. This study demonstrated how a CNCCs-originated ligand impaired tongue myogenesis via a non-autonomous way, which provided potential formation mechanisms for understanding tongue abnormalities in CNC-related syndromes.

舌肌来源于中胚层细胞，而由颅神经嵴细胞 (CNCC) 驱动的信号通过组织-组织相互作用调节舌肌生成。基于这种相互作用机制，先天性舌缺陷发生在人类的 CNC 相关综合征中。本研究利用先天性骨性合颌综合征的病理模型Wnt1-Cre;pMes-Bmp4小鼠系，探索增强的 CNCCs 来源的 BMP4 信号通过组织-组织相互作用对舌肌生成的影响。我们的研究结果表明，在Wnt1-Cre;pMes-Bmp4中表现出人类先天性骨性合颌的临床表型 microglossia小鼠由于肌生成受损。增强的 BMP4 信号影响肌原细胞的远端分布、增殖和分化以及肌腱模式，导致舌肌紊乱和萎缩以及前二腹肌的丧失。本研究展示了 CNCCs 来源的配体如何通过非自主方式损害舌肌生成，这为理解 CNC 相关综合征中的舌异常提供了潜在的形成机制。