Szarama Katherine B, Gavara Núria, Petralia Ronald S, Chadwick Richard S, Kelley Matthew W
Section on Developmental Neuroscience, Laboratory of Cochlear Development, National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, MD, USA.
BMC Dev Biol. 2013 Feb 9;13:6. doi: 10.1186/1471-213X-13-6.
Thyroid hormones regulate growth and development. However, the molecular mechanisms by which thyroid hormone regulates cell structural development are not fully understood. The mammalian cochlea is an intriguing system to examine these mechanisms, as cellular structure plays a key role in tissue development, and thyroid hormone is required for the maturation of the cochlea in the first postnatal week.
In hypothyroid conditions, we found disruptions in sensory outer hair cell morphology and fewer microtubules in non-sensory supporting pillar cells. To test the functional consequences of these cytoskeletal defects on cell mechanics, we combined atomic force microscopy with live cell imaging. Hypothyroidism stiffened outer hair cells and supporting pillar cells, but pillar cells ultimately showed reduced cell stiffness, in part from a lack of microtubules. Analyses of changes in transcription and protein phosphorylation suggest that hypothyroidism prolonged expression of fibroblast growth factor receptors, and decreased phosphorylated Cofilin.
These findings demonstrate that thyroid hormones may be involved in coordinating the processes that regulate cytoskeletal dynamics and suggest that manipulating thyroid hormone sensitivity might provide insight into the relationship between cytoskeletal formation and developing cell mechanical properties.
甲状腺激素调节生长和发育。然而，甲状腺激素调节细胞结构发育的分子机制尚未完全明确。哺乳动物的耳蜗是研究这些机制的一个有趣系统，因为细胞结构在组织发育中起关键作用，且出生后第一周耳蜗的成熟需要甲状腺激素。
在甲状腺功能减退的情况下，我们发现感觉性外毛细胞形态出现破坏，非感觉性支持柱细胞中的微管减少。为了测试这些细胞骨架缺陷对细胞力学的功能影响，我们将原子力显微镜与活细胞成像相结合。甲状腺功能减退使外毛细胞和支持柱细胞变硬，但柱细胞最终显示细胞硬度降低，部分原因是缺乏微管。对转录和蛋白质磷酸化变化的分析表明，甲状腺功能减退延长了成纤维细胞生长因子受体的表达，并降低了磷酸化丝切蛋白。
这些发现表明，甲状腺激素可能参与协调调节细胞骨架动力学的过程，并表明操纵甲状腺激素敏感性可能有助于深入了解细胞骨架形成与发育中细胞力学特性之间的关系。
