Loss of R-spondin2 Leads to Excess Hair Cell Development in the Mammalian Cochlea

Recent studies have demonstrated the importance of R- spondins, a novel family of secreted proteins, in canonical Wnt signaling and FGF signaling, two pathways that play significant roles in the development of the cochlea, the hearing organ. Cochlear development requires several events including growth, proliferation and cell fate specification. Furthermore, normal cellular patterning in the cochlea, the organ of Corti, is crucial for auditory function as any patterning defects result in hearing deficit. R- spondins (Rspo) consist of four members in mammals encoded by separate genes. To begin to investigate a possible role in cochlear development, the expression of all Rspo members was assayed at the time of mechanosensory hair cell differentiation. Rspo2 and Rspo3 were detected by PCR but not Rspo1 or Rspo4. The role of Rspo2 in the development of the mouse cochlea was investigated in this study by examining the Rspo2-/- mice. Within the organ of Corti, a single row of inner hair cells and three rows of outer hair cells extend along the basal-to-apical axis of the cochlea. Every sensory hair cell is separated from the next by an intervening non- sensory supporting cell resulting in an invariant mosaic. In the Rspo2 mutant cochleae, there was an extra row of outer hair cells along with an extra row of support cells in the apical half of the cochlea. These data suggest that R-spondin2 is involved in cell fate determination in the mammalian cochlea