Phosphatase and tensin homolog deleted on chromosome 10 regulates sensory cell proliferation and differentiation of hair bundles in the mammalian cochlea.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor gene that regulates cell proliferation, differentiation and growth. It regulates neural and glioma stem/progenitor cell renewal and PTEN deletion can drive expansion of epithelial progenitors in the lung, enhancing their capacity for regeneration. Because it is expressed at relatively high levels in developing mammalian auditory hair cells we have analyzed the phenotype of the auditory epithelium in PTEN knock-out mice. PTEN(+/-) heterozygous littermates have only one functional copy of the gene and show clear evidence for haploinsufficiency in the organ of Corti. Auditory sensory epithelial progenitors withdraw from the cell cycle later than in wild-type animals and this is associated with increases in the numbers of both inner and outer hair cells. The cytoskeletal differentiation of hair cells was also affected. While many hair bundles on the hair cells appeared to develop normally, others were structurally disorganized and a number were missing, apparently lost after they had been formed. The results show that PTEN plays a novel role in regulating cell proliferation and differentiation of hair bundles in auditory sensory epithelial cells and suggest that PTEN signaling pathways may provide therapeutic targets for auditory sensory regeneration.