Developmental genetic bases behind the independent origin of the tympanic membrane in mammals and diapsids

Nat Commun. 2015 Apr 22;6:6853. doi: 10.1038/ncomms7853.


The amniote middle ear is a classical example of the evolutionary novelty. Although paleontological evidence supports the view that mammals and diapsids (modern reptiles and birds) independently acquired the middle ear after divergence from their common ancestor, the developmental bases of these transformations remain unknown. Here we show that lower-to-upper jaw transformation induced by inactivation of the Endothelin1-Dlx5/6 cascade involving Goosecoid results in loss of the tympanic membrane in mouse, but causes duplication of the tympanic membrane in chicken. Detailed anatomical analysis indicates that the relative positions of the primary jaw joint and first pharyngeal pouch led to the coupling of tympanic membrane formation with the lower jaw in mammals, but with the upper jaw in diapsids. We propose that differences in connection and release by various pharyngeal skeletal elements resulted in structural diversity, leading to the acquisition of the tympanic membrane in two distinct manners during amniote evolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ambystoma mexicanum / embryology*
  • Ambystoma mexicanum / genetics
  • Animals
  • Base Sequence
  • Embryo, Mammalian
  • Embryo, Nonmammalian
  • Endothelin-1 / genetics*
  • Endothelin-1 / metabolism
  • Evolution, Molecular
  • Gene Expression Regulation, Developmental
  • Goosecoid Protein / genetics
  • Goosecoid Protein / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Lizards / embryology*
  • Lizards / genetics
  • Mandible / embryology
  • Maxilla / embryology
  • Mice / embryology*
  • Mice / genetics
  • Molecular Sequence Data
  • Paired Box Transcription Factors / genetics
  • Paired Box Transcription Factors / metabolism
  • Receptor, Endothelin A / genetics*
  • Receptor, Endothelin A / metabolism
  • Sharks / embryology*
  • Sharks / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Tympanic Membrane / embryology*


  • Dlx5 protein, mouse
  • Dlx6 protein, mouse
  • Endothelin-1
  • Goosecoid Protein
  • Homeodomain Proteins
  • Nkx3-2 protein, mouse
  • Paired Box Transcription Factors
  • Receptor, Endothelin A
  • Transcription Factors
  • PAX1 transcription factor

Associated data

  • GENBANK/AB985798