Loss of liver kinase B1 causes planar polarity defects in cochlear hair cells in mice  

作　　者：Yuqin Men Aizhen Zhang Liwen Zhang Yecheng Jin Zhishuo Wang Jing Zhao Xiaolin Yu Jian Zhang Jiangang Gao 

机构地区：[1]Sehool of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan 250100, China [2]jinan First People's Hospital, Jinan 250011, China

出　　处：《Frontiers of Medicine》2016年第4期481-489,共9页医学前沿（英文版）

基　　金：This work was supported by grants from the National Basic Research Program （973） of China （No. 2014CB541703）; the National Natural Science Foundation of China （Nos. 30871436, 30973297, 31171194, and 81670943）; the Shandong Provincial Science and Technology Key Program （No. 2009GG10002039）; and the Shandong Provincial Natural Science Foundation of China Grant （No. ZR2013CQ041）.

摘　　要：The tumor suppressor gene liver kinase B1 （LKB1）, also called STKll, encodes a serine/threonine kinase. LKB1 plays crucial roles in cell differentiation, proliferation, and polarity. In this study, LKB1 conditional knockout mice （LKB1pax2 CKO mice） were generated using Pax2-Cre mice to investigate the function of LKB1 in inner ear hair cells during early embryonic period. LKB1Pax2 CKO mice died perinatally. Immunofluorescence and scanning electron microscopy revealed that stereociliary bundles in LKB1Pax2 CKO mice were clustered and misoriented, respectively. Moreover, ectopic distribution of kinocilium bundles resulting from abnormal migration of kinocilium was observed in the mutant mice. The orientation of stereociliary bundles and the migration of kinocilia are critical indicators of planar cell polarity （PCP） of hair cells. LKB1 deficiency in LKB1Pax2 CKO mice thus disrupted hair cell planar polarity during embryonic development. Our results suggest that LKB1 is required in PCP formation in cochlear hair cells in mice.The tumor suppressor gene liver kinase B1 （LKB1）, also called STKll, encodes a serine/threonine kinase. LKB1 plays crucial roles in cell differentiation, proliferation, and polarity. In this study, LKB1 conditional knockout mice （LKB1pax2 CKO mice） were generated using Pax2-Cre mice to investigate the function of LKB1 in inner ear hair cells during early embryonic period. LKB1Pax2 CKO mice died perinatally. Immunofluorescence and scanning electron microscopy revealed that stereociliary bundles in LKB1Pax2 CKO mice were clustered and misoriented, respectively. Moreover, ectopic distribution of kinocilium bundles resulting from abnormal migration of kinocilium was observed in the mutant mice. The orientation of stereociliary bundles and the migration of kinocilia are critical indicators of planar cell polarity （PCP） of hair cells. LKB1 deficiency in LKB1Pax2 CKO mice thus disrupted hair cell planar polarity during embryonic development. Our results suggest that LKB1 is required in PCP formation in cochlear hair cells in mice.

关 键 词：LKB1 stereociliary bundles kinocilium planar cell polarity HEARING MICE 

分 类 号：R[医药卫生]