Testin interacts with vangl2 genetically to regulate inner ear sensory cell orientation and the normal development of the female reproductive tract in mice.

Testin interacts with vangl2 genetically to regulate inner ear sensory cell orientation and the normal development of the female reproductive tract in mice.
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DOI:
10.1002/dvdy.24042
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发表时间:
2013-12
影响因子:
2.5
通讯作者:
Chen, Ping
Chen, Ping
中科院分区:
生物学3区
文献类型:
--
作者:
Ren, Dong-Dong;Kelly, Michael;Kim, Sun Myoung;Grimsley-Myers, Cynthia Mary;Chi, Fang-Lu;Chen, Ping

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平面细胞极性(PCP)信号调节细胞的协调极化,是许多组织正常发育和功能所必需的。先前的研究已经发现了保守的PCP基因,如Van gogh-like 2 (Vangl2)和Prickle (Pk),它们在内耳毛细胞的协调定向和雌性生殖道发育中起调节作用。testn与Pk具有PET-LIM同源性。目前尚不清楚testn是否在哺乳动物PCP过程中起作用。我们通过耳蜗cDNA文库的2-杂交筛选,鉴定出testn是一个与vangl2相互作用的蛋白。在培养的细胞中,在有Vangl2存在的情况下,睾丸被富集到细胞-细胞边界。睾丸基因失活导致前庭毛细胞定向异常和耳蜗细胞模式缺陷。此外,睾丸素与Vangl2基因相互作用,调节耳蜗毛细胞取向和阴道开口。我们的研究结果表明,睾丸素是一个参与内耳毛细胞定向协调和女性生殖道发育的基因。此外,它与Vangl2的遗传相互作用暗示它是一个潜在的分子链接,负责介导含Vangl2的膜PCP复合物在指导形态极化中的作用。
Planar cell polarity (PCP) signaling regulates the coordinated polarization of cells and is required for the normal development and function of many tissues. Previous studies have identified conserved PCP genes, such as Van gogh-like 2 (Vangl2) and Prickle (Pk), in the regulation of coordinated orientation of inner ear hair cells and female reproductive tract development. Testin shares a PET-LIM homology with Pk. It is not clear whether Testin acts in PCP processes in mammals. We identified Testin as a Vangl2-interacting protein through a 2-hybrid screen with a cochlea cDNA library. Testin is enriched to cell-cell boundaries in the presence of Vangl2 in cultured cells. Genetic inactivation of Testin leads to abnormal hair cell orientation in the vestibule and cellular patterning defects in the cochlea. In addition, Testin genetically interacts with Vangl2 to regulate hair cell orientation in the cochlea and the opening of the vaginal tract. Our findings suggested Testin as a gene involved in coordinated hair cell orientation in the inner ear and in female reproductive tract development. Furthermore, its genetic interaction with Vangl2 implicated it as a potential molecular link, responsible for mediating the role of Vangl2-containing membranous PCP complexes in directing morphologic polarization.
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