title: 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 (LKB1Pax2CKO mice) were generated using Pax2-Cre mice to investigate the function of LKB1 in inner ear hair cells during early embryonic period. LKB1Pax2CKO mice died perinatally. Immunofluorescence and scanning electron microscopy revealed that stereociliary bundles in LKB1Pax2CKO 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 LKB1Pax2CKO 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.
authors.affiliation: School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan, 250100, China.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Men
authors.affiliation: School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan, 250100, China.
authors.forename: Aizhen
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Jinan First People's Hospital, Jinan, 250011, China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan, 250100, China.
authors.forename: Yecheng
authors.initials: Y
authors.lastname: Jin
authors.affiliation: School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan, 250100, China.
authors.forename: Zhishuo
authors.initials: Z
authors.lastname: Wang
authors.affiliation: School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan, 250100, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Jinan First People's Hospital, Jinan, 250011, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Yu
authors.affiliation: School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan, 250100, China. zhj8226@sdu.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan, 250100, China. jggao@sdu.edu.cn.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Gao
mesh_terms: D055372:AMP-Activated Protein Kinases; D000818:Animals; D002454:Cell Differentiation; D016764:Cell Polarity; D002923:Cilia / Q000473:pathology / Q000648:ultrastructure*; D005260:Female; D006198:Hair Cells, Auditory / Q000473:pathology / Q000648:ultrastructure*; D051379:Mice; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases
keywords: LKB1; hearing; kinocilium; mice; planar cell polarity; stereociliary bundles