Yang Tian, Kersigo Jennifer, Wu Shu, Fritzsch Bernd, Bassuk Alexander G
Department of Biology, University of Iowa, Iowa City, Iowa, United States of America.
Department of Pediatrics, University of Iowa, Iowa City, Iowa, United States of America.
PLoS One. 2017 Aug 24;12(8):e0183773. doi: 10.1371/journal.pone.0183773. eCollection 2017.
In the mammalian organ of Corti (OC), the stereocilia on the apical surface of hair cells (HCs) are uniformly organized in a neural to abneural axis (or medial-laterally). This organization is regulated by planar cell polarity (PCP) signaling. Mutations of PCP genes, such as Vangl2, Dvl1/2, Celsr1, and Fzd3/6, affect the formation of HC orientation to varying degrees. Prickle1 is a PCP signaling gene that belongs to the prickle / espinas / testin family. Prickle1 protein is shown to be asymmetrically localized in the HCs of the OC, and this asymmetric localization is associated with loss of PCP in Smurf mutants, implying that Prickle1 is involved in HC PCP development in the OC. A follow-up study found no PCP polarity defects after loss of Prickle1 (Prickle1-/-) in the cochlea. We show here strong Prickle1 mRNA expression in the spiral ganglion by in situ hybridization and β-Gal staining, and weak expression in the OC by β-Gal staining. Consistent with this limited expression in the OC, cochlear HC PCP is unaffected in either Prickle1C251X/C251X mice or Prickle1f/f; Pax2-cre conditional null mice. Meanwhile, type II afferents of apical spiral ganglion neurons (SGN) innervating outer hair cells (OHC) have unusual neurite growth. In addition, afferents from the apex show unusual collaterals in the cochlear nuclei that overlap with basal turn afferents. Our findings argue against the role of Prickle1 in regulating hair cell polarity in the cochlea. Instead, Prickle1 regulates the polarity-related growth of distal and central processes of apical SGNs.
在哺乳动物的柯蒂氏器（OC）中，毛细胞（HC）顶表面的静纤毛沿神经到反神经轴（或内侧到外侧）均匀排列。这种排列受平面细胞极性（PCP）信号通路调控。PCP基因（如Vangl2、Dvl1/2、Celsr1和Fzd3/6）的突变会不同程度地影响HC方向的形成。Prickle1是一个属于Prickle / Espinas / Testin家族的PCP信号基因。已证明Prickle1蛋白在OC的HC中不对称定位，并且这种不对称定位与Smurf突变体中PCP的丧失有关，这意味着Prickle1参与了OC中HC PCP的发育。一项后续研究发现，耳蜗中Prickle1缺失（Prickle1-/-）后没有PCP极性缺陷。我们通过原位杂交和β-半乳糖苷酶染色显示螺旋神经节中有强烈的Prickle1 mRNA表达，通过β-半乳糖苷酶染色显示OC中有微弱表达。与在OC中的这种有限表达一致，在Prickle1C251X/C251X小鼠或Prickle1f/f; Pax2-cre条件性敲除小鼠中，耳蜗HC PCP均未受影响。同时，支配外毛细胞（OHC）的顶螺旋神经节神经元（SGN）的II型传入神经有异常的神经突生长。此外，来自顶端的传入神经在耳蜗核中显示出与基底转弯传入神经重叠的异常侧支。我们的研究结果反对Prickle1在调节耳蜗毛细胞极性中的作用。相反，Prickle1调节顶SGN远端和中央突起的极性相关生长。
