The ciliary protein C2cd3 is required for mandibular musculoskeletal tissue patterning

Differentiation. 2024 Jul-Aug:138:100782. doi: 10.1016/j.diff.2024.100782. Epub 2024 May 23.

Abstract

The mandible is composed of several musculoskeletal tissues including bone, cartilage, and tendon that require precise patterning to ensure structural and functional integrity. Interestingly, most of these tissues are derived from one multipotent cell population called cranial neural crest cells (CNCCs). How CNCCs are properly instructed to differentiate into various tissue types remains nebulous. To better understand the mechanisms necessary for the patterning of mandibular musculoskeletal tissues we utilized the avian mutant talpid2 (ta2) which presents with several malformations of the facial skeleton including dysplastic tendons, mispatterned musculature, and bilateral ectopic cartilaginous processes extending off Meckel's cartilage. We found an ectopic epithelial BMP signaling domain in the ta2 mandibular prominence (MNP) that correlated with the subsequent expansion of SOX9+ cartilage precursors. These findings were validated with conditional murine models suggesting an evolutionarily conserved mechanism for CNCC-derived musculoskeletal patterning. Collectively, these data support a model in which cilia are required to define epithelial signal centers essential for proper musculoskeletal patterning of CNCC-derived mesenchyme.

Keywords: C2CD3; Craniofacial development; Enthesis; Mandible; Primary cilia; talpid(2).

MeSH terms

  • Animals
  • Avian Proteins / genetics
  • Avian Proteins / metabolism
  • Body Patterning / genetics
  • Cartilage / cytology
  • Cartilage / growth & development
  • Cartilage / metabolism
  • Cell Differentiation
  • Chick Embryo
  • Chickens / genetics
  • Cilia / genetics
  • Cilia / metabolism
  • Gene Expression Regulation, Developmental
  • Mandible* / growth & development
  • Mandible* / metabolism
  • Mesoderm / cytology
  • Mesoderm / growth & development
  • Mesoderm / metabolism
  • Mice
  • Neural Crest* / cytology
  • Neural Crest* / metabolism
  • SOX9 Transcription Factor / genetics
  • SOX9 Transcription Factor / metabolism
  • Signal Transduction

Substances

  • Avian Proteins
  • SOX9 Transcription Factor
  • C2cd3 protein, mouse