Cdo regulates pillar cell formation in cochlea as transmembrane receptor of Shh signaling

Abstract

Transmembrane glycoproteins Cdo bind directly to Shh and other receptor components like Boc, Gas1 and ptch1 as an essential receptor to positively regulate Shh signaling. To investigate the specific effects of Cdo on sensory epithelium of embryonic cochlea development, we inactivated Cdo in embryonic cochlear via transgenetic mice. Results indicated that ectopic hair cells were exhibited and pillar cells were lost in the E16.5 Cdo mutant cochlea. Besides, supernumerary inner hair cells were observed when reduce one allele of Shh in Cdo mutant in E18.5. Then we investigated Ptch1 expression as a Hh signaling readout and Ptch1 was reduced in the apical region of the cochlea duct. Meanwhile we examined the mRNA expression of coreceptors Boc and Gas1 via in situ hybridization, and found that the expression of Boc was enhanced and Gas1 was reduce especially in apex of Cdo mutant respectively. To study whether Cdo is involved in regulating pillar cell through FGF signaling, Fgf8 mRNA expression level was examined and it was reduced dramatically in Cdo mutant cochlea. These results illustrate significate and diverse roles for Cdo in the development and specification of hair cells and pillar cells within the cochlea during embryonic period. The project is ethically approved for animal studies.