Blinkiewicz Paige V, Long Makayla R, Stoner Zachary A, Ketchum Elizabeth M, Sheltz-Kempf Sydney N, Duncan Jeremy S
Western Michigan University.
Res Sq. 2023 Apr 14:rs.3.rs-2747944. doi: 10.21203/rs.3.rs-2747944/v1.
It has been previously shown that zinc-finger transcription factor has dynamic expression within the inner ear throughout embryonic development and is essential for cochlear neurosensory development. However, the temporal window to which is required for the formation of the cochlear neurosensory epithelia remains unclear. To investigate the role of on cochlear neurosensory development in the late prosensory stages, we used the mouse line to target and conditionally delete at E11.5 before the cells have fully committed to a neurosensory fate. While the inner ears of mice appear morphologically normal, the sensory cells in the organ of Corti are partially lost and disorganized in a basal to apical gradient with the apex demonstrating the more severe phenotype. Additionally, spiral ganglion neurons display aberrant peripheral projections, such as increased distances between radial bundles and disorganization upon reaching the organ of Corti. Furthermore, heterozygous mice show a reduced phenotype in comparison to the homozygous mutant, supporting the concept that is not only required for proper formation at the later proneurosensory stage, but also that a specific level of is required. Therefore, our studies confirm that plays a time-sensitive and dose-dependent role in the development of sensory cells in the late proneurosensory stages.
先前的研究表明，锌指转录因子在整个胚胎发育过程中在内耳中具有动态表达，并且对耳蜗神经感觉发育至关重要。然而，耳蜗神经感觉上皮形成所需的时间窗口仍不清楚。为了研究锌指转录因子在感觉前体后期阶段对耳蜗神经感觉发育的作用，我们使用了一种小鼠品系，在细胞完全确定为神经感觉命运之前的E11.5期靶向并条件性删除锌指转录因子。虽然该小鼠品系的内耳在形态上看起来正常，但柯蒂氏器中的感觉细胞部分丢失，并以从基部到顶部的梯度方式排列紊乱，顶部表现出更严重的表型。此外，螺旋神经节神经元显示出异常的外周投射，例如径向束之间的距离增加以及到达柯蒂氏器时排列紊乱。此外，与纯合突变体相比，杂合小鼠表现出减轻的表型，这支持了锌指转录因子不仅在后期感觉前体阶段的正常形成中是必需的，而且还需要特定水平的锌指转录因子这一概念。因此，我们的研究证实，锌指转录因子在感觉前体后期阶段的感觉细胞发育中发挥着时间敏感和剂量依赖的作用。
