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

Abstract

The tumor suppressor gene liver kinase B1 (LKB1), also called STK11, encodes a serine/threonine kinase. LKB1 plays crucial roles in cell differentiation, proliferation, and polarity. In this study, LKB1 conditional knockout mice (LKB1^Pax2 CKO mice) were generated using Pax2-Cre mice to investigate the function of LKB1 in inner ear hair cells during early embryonic period. LKB1^Pax2 CKO mice died perinatally. Immunofluorescence and scanning electron microscopy revealed that stereociliary bundles in LKB1^Pax2 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 LKB1^Pax2 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.

Keywords

LKB1 / stereociliary bundles / kinocilium / planar cell polarity / hearing / mice

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Acknowledgements

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).

Compliance with ethics guidelines

Yuqin Men, Aizhen Zhang, Liwen Zhang, Yecheng Jin, Zhishuo Wang, Jing Zhao, Xiaolin Yu, Jian Zhang, and Jiangang Gao declare that they have no conflict of interest. All institutional and national guidelines for the care and use of laboratory animals were followed. Animal management and use were strictly in accordance with the standards of the Animal Ethics Committee of Shandong University. All animal experimental procedures were approved by Ethics Committee of Shandong University.

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