Functional analysis of the PI3K/Akt signaling pathway during the mammalian inner ear development and its application for regenerative medicine

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PTEN, a product of a tumor suppressor gene, inhibits the PI3K/Akt pathway by dephosphorylating phosphatidylinositol (3,4,5)-triphosphate. We tried to elucidate the functions of PTEN during mammalian cochlear development by deleting PTEN conditionally in the mouse inner ear.In PTEN-conditional knockout (cko) mutant cochlea, the diameter of cochlear ducts was increased and the cell proliferation continued till the later stage outside of the prosensory region. Extra rows of OHCs and IHCs were observed, whereas the average length of the cochlear ducts was shorter than that of the control mice. The expression patterns of early prosensory markers were almost same between the PTEN-CKO and the control mice. However, the hair cell differentiation was accelerated in the PTEN-CKO cochleae. The results indicate that PTEN may regulate the cell differentiation and proliferation after the prosensory determination, and contribute to the convergent extension of the cochlear duct.