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

PTEN是一种肿瘤抑制基因的产物，通过使磷脂酰肌醇（3，4，5）-三磷酸去磷酸化来抑制PI 3 K/Akt通路。为了阐明PTEN在哺乳动物耳蜗发育中的作用，我们在小鼠内耳中条件性地敲除了PTEN基因，结果发现，在PTEN条件性敲除（cko）的小鼠耳蜗中，耳蜗导管直径增大，细胞增殖持续到感觉区以外的晚期。观察到OHC和IHC的额外行，而耳蜗管的平均长度比对照小鼠短。PTEN-CKO组小鼠和对照组小鼠的早期前感觉标记物的表达模式几乎相同。而在耳蜗中，PTEN-CKO毛细胞分化加快。结果提示，PTEN可能在耳蜗前感觉决定后调节细胞的分化和增殖，并参与耳蜗导管的会聚性伸展。

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.