Signals from the brain and olfactory epithelium control shaping of the mammalian nasal capsule cartilage

Elife. 2018 Jun 13;7:e34465. doi: 10.7554/eLife.34465.

Abstract

Facial shape is the basis for facial recognition and categorization. Facial features reflect the underlying geometry of the skeletal structures. Here, we reveal that cartilaginous nasal capsule (corresponding to upper jaw and face) is shaped by signals generated by neural structures: brain and olfactory epithelium. Brain-derived Sonic Hedgehog (SHH) enables the induction of nasal septum and posterior nasal capsule, whereas the formation of a capsule roof is controlled by signals from the olfactory epithelium. Unexpectedly, the cartilage of the nasal capsule turned out to be important for shaping membranous facial bones during development. This suggests that conserved neurosensory structures could benefit from protection and have evolved signals inducing cranial cartilages encasing them. Experiments with mutant mice revealed that the genomic regulatory regions controlling production of SHH in the nervous system contribute to facial cartilage morphogenesis, which might be a mechanism responsible for the adaptive evolution of animal faces and snouts.

Keywords: cartilage induction; cleft palate; developmental biology; embryonic development; facial shaping; mammalian face; mouse; regenerative medicine; sonic hedgehog; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / growth & development
  • Brain / metabolism*
  • Chondrocytes / cytology
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism*
  • Collagen Type II / genetics
  • Collagen Type II / metabolism
  • Embryo, Mammalian
  • Face / anatomy & histology
  • Face / embryology
  • Facial Bones / cytology
  • Facial Bones / drug effects
  • Facial Bones / growth & development
  • Facial Bones / metabolism
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins / genetics*
  • Hedgehog Proteins / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Integrases / genetics
  • Integrases / metabolism
  • Maxillofacial Development / genetics*
  • Mice
  • Mice, Transgenic
  • Morphogenesis / drug effects
  • Morphogenesis / genetics*
  • Mutagens / administration & dosage
  • Nasal Cartilages / cytology
  • Nasal Cartilages / drug effects
  • Nasal Cartilages / growth & development
  • Nasal Cartilages / metabolism
  • Olfactory Mucosa / cytology
  • Olfactory Mucosa / drug effects
  • Olfactory Mucosa / growth & development
  • Olfactory Mucosa / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction*
  • Tamoxifen / administration & dosage
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Zebrafish Proteins

Substances

  • Col2a1 protein, mouse
  • Collagen Type II
  • Hedgehog Proteins
  • Homeodomain Proteins
  • Mutagens
  • Nkx2.2 protein
  • Recombinant Fusion Proteins
  • SHH protein, human
  • Transcription Factors
  • Zebrafish Proteins
  • Tamoxifen
  • Cre recombinase
  • Integrases