Dynamic activation of Wnt, Fgf, and Hh signaling during soft palate development

PLoS One. 2019 Oct 15;14(10):e0223879. doi: 10.1371/journal.pone.0223879. eCollection 2019.


The soft palate is a key component of the oropharyngeal complex that is critical for swallowing, breathing, hearing and speech. However, complete functional restoration in patients with cleft soft palate remains a challenging task. New insights into the molecular signaling network governing the development of soft palate will help to overcome these clinical challenges. In this study, we investigated whether key signaling pathways required for hard palate development are also involved in soft palate development in mice. We described the dynamic expression patterns of signaling molecules from well-known pathways, such as Wnt, Hh, and Fgf, during the development of the soft palate. We found that Wnt signaling is active throughout the development of soft palate myogenic sites, predominantly in cells of cranial neural crest (CNC) origin neighboring the myogenic cells, suggesting that Wnt signaling may play a significant role in CNC-myogenic cell-cell communication during myogenic differentiation in the soft palate. Hh signaling is abundantly active in early palatal epithelium, some myogenic cells, and the CNC-derived cells adjacent to the myogenic cells. Hh signaling gradually diminishes during the later stages of soft palate development, indicating its involvement mainly in early embryonic soft palate development. Fgf signaling is expressed most prominently in CNC-derived cells in the myogenic sites and persists until later stages of embryonic soft palate development. Collectively, our results highlight a network of Wnt, Hh, and Fgf signaling that may be involved in the development of the soft palate, particularly soft palate myogenesis. These findings provide a foundation for future studies on the functional significance of these signaling pathways individually and collectively in regulating soft palate development.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Communication
  • Fibroblast Growth Factors / metabolism*
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins / metabolism*
  • Mice
  • Muscle Development
  • Neural Crest / cytology
  • Neural Crest / metabolism
  • Palate, Soft / growth & development*
  • Palate, Soft / metabolism
  • Signal Transduction
  • Wnt Proteins / metabolism*


  • Hedgehog Proteins
  • Wnt Proteins
  • Fibroblast Growth Factors