啮齿动物出生后12天才有听觉，与之对应的是耳蜗大上皮嵴消失。大上皮嵴的支持细胞通过缝隙连接蛋白（Cx26和/或Cx30）形成功能性合胞体，但其如何促进耳蜗发育成熟及其调控机制不明确。申请人长期致力于三磷酸腺苷（ATP）与耳蜗发育关系的研究，首次获得大上皮嵴支持细胞释放ATP的直接证据，证明耳蜗血管纹缘细胞内ATP贮存囊泡为溶酶体，耳蜗中ATP合成、降解、释放、作用通路上相关蛋白间存在相互作用，发现大上皮嵴支持细胞不仅有凋亡也有自噬。我们假设大上皮嵴支持细胞在哺乳动物耳蜗发育中发挥非常关键的作用，本项目拟观察模型动物Cx26sox10Cre和Cx30(-/-)小鼠大上皮嵴支持细胞凋亡/自噬，以及内毛细胞、突触、螺旋神经元形态功能的变化，大上皮嵴中邻近内毛细胞的支持细胞与其它细胞形态和功能有何不同，以及证明支持细胞内贮存ATP的囊泡是溶酶体。本研究对进一步阐明外周听器的发育机制有重要意义。

Rodent has not hearing until 12 days after birth, which corresponds to the apoptosis of the greater epithelial ridge (GER) in the cochlea. Supporting cells within GER form a functional syncytium through connexin 26 and/or 30, however, how they promote cochlear maturation and its regulatory mechanism still remains unclear. We have long been engaged in the research of the relationship between ATP and cochlear development and are the first to get direct evidence of ATP release from supporting cells in GER. We found for the first time that the expression of mRNA and protein of apoptosis related factors is time-dependent, ATP-containing vesicles within marginal cells in the stria vascularis are lysosomes, and there are interactions among related proteins in the pathway of ATP synthesis, degradation, release and action in the cochlea. We found that not only apoptosis but also autophagy of the supporting cells exists in GER. We assume that supporting cells in GER play a crucial role in the development of the mammalian cochlea. To substantiate this assumption, the present research will observe the apoptosis or autophagy of supporting cells, morphological and functional changes in inner hair cells, synapsis and spiral ganglion neurons in Cx26sox10Cre and Cx30 (-/-) mice, the morphological and functional differences between the supporting cells adjacent to the inner hair cells and other cells within GER, and whether the ATP-containing vesicles in the supporting cell are lysosomes. The present research has profound significance for the further elucidation of the developmental mechanism of the peripheral auditory organ.