Hedgehog signaling patterns the oral-aboral axis of the mandibular arch

Elife. 2019 Jan 14:8:e40315. doi: 10.7554/eLife.40315.

Abstract

Development of vertebrate jaws involves patterning neural crest-derived mesenchyme cells into distinct subpopulations along the proximal-distal and oral-aboral axes. Although the molecular mechanisms patterning the proximal-distal axis have been well studied, little is known regarding the mechanisms patterning the oral-aboral axis. Using unbiased single-cell RNA-seq analysis followed by in situ analysis of gene expression profiles, we show that Shh and Bmp4 signaling pathways are activated in a complementary pattern along the oral-aboral axis in mouse embryonic mandibular arch. Tissue-specific inactivation of hedgehog signaling in neural crest-derived mandibular mesenchyme led to expansion of BMP signaling activity to throughout the oral-aboral axis of the distal mandibular arch and subsequently duplication of dentary bone in the oral side of the mandible at the expense of tongue formation. Further studies indicate that hedgehog signaling acts through the Foxf1/2 transcription factors to specify the oral fate and pattern the oral-aboral axis of the mandibular mesenchyme.

Keywords: BMP; craniofacial; developmental biology; mandible; mouse; neural crest; pattern formation; single-cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning
  • Bone Morphogenetic Protein 4 / physiology
  • Bone Morphogenetic Proteins / physiology
  • Cluster Analysis
  • Female
  • Forkhead Transcription Factors / physiology
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Hedgehog Proteins / physiology*
  • Male
  • Mandible / embryology*
  • Mandible / growth & development*
  • Mesoderm / cytology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Crest / physiology
  • Sequence Analysis, RNA
  • Signal Transduction*
  • Tongue / embryology
  • Tongue / growth & development

Substances

  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • Forkhead Transcription Factors
  • Foxf1 protein, mouse
  • Foxf2 protein, mouse
  • Hedgehog Proteins
  • Shh protein, mouse