Temporal and spatial expression patterns of Hedgehog receptors in the developing inner and middle ear

Int J Dev Biol. 2017;61(8-9):557-563. doi: 10.1387/ijdb.170155jb.


The mammalian inner ear is a complex organ responsible for balance and hearing. Sonic hedgehog (Shh), a member of the Hedgehog (Hh) family of secreted proteins, has been shown to play important roles in several aspects of inner ear development, including dorsoventral axial specification, cochlear elongation, tonotopic patterning, and hair cell differentiation. Hh proteins initiate a downstream signaling cascade by binding to the Patched 1 (Ptch1) receptor. Recent studies have revealed that other types of co-receptors can also mediate Hh signaling, including growth arrest-specific 1 (Gas1), cell-adhesion molecules-related/down-regulated by oncogenes (Cdon), and biregional Cdon binding protein (Boc). However, little is known about the role of these Hh co-receptors in inner ear development. In this study, we examined the expression patterns of Gas1, Cdon, and Boc, as well as that of Ptch1, in the developing mouse inner ear from otocyst (embryonic day (E) 9.5) until birth and in the developing middle ear at E15.5. Ptch1, a readout of Hh signaling, was expressed in a graded pattern in response to Shh signaling throughout development. Expression patterns of Gas1, Cdon, and Boc differed from that of Ptch1, and each Hh co-receptor was expressed in specific cells and domains in the developing inner and middle ear. These unique and differential expression patterns of Hh co-receptors suggest their roles in mediating various time- and space-specific functions of Shh during ear development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion Molecules / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Ear, Inner / cytology
  • Ear, Inner / metabolism*
  • Ear, Middle / cytology
  • Ear, Middle / metabolism*
  • Female
  • GPI-Linked Proteins / metabolism
  • Hedgehog Proteins / metabolism*
  • Immunoglobulin G / metabolism*
  • Mice
  • Mice, Inbred ICR
  • Neurogenesis / physiology
  • Patched-1 Receptor / metabolism*
  • Pregnancy
  • Receptors, Cell Surface / metabolism*
  • Signal Transduction


  • Boc protein, mouse
  • Cdon protein, mouse
  • Cell Adhesion Molecules
  • Cell Cycle Proteins
  • GPI-Linked Proteins
  • Gas1 protein, mouse
  • Hedgehog Proteins
  • Immunoglobulin G
  • Patched-1 Receptor
  • Ptch1 protein, mouse
  • Receptors, Cell Surface
  • Shh protein, mouse