Thyroid hormone increases fibroblast growth factor receptor expression and disrupts cell mechanics in the developing organ of corti
1 Section on Developmental Neuroscience, Laboratory of Cochlear Development, National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, MD, USA
2 Section on Auditory Mechanics, Laboratory of Cellular Biology, National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, MD, USA
3 Center for Hearing and Communication Research and Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden
4 Advanced Imaging Core, National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, MD, USA
5 Current address: Laboratory of Joseph Opferman, Department of Biochemistry, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105-3678, USA
6 Current address: Drittes Physikalisches Institut, Georg-August-Univesität, Göttingen, Germany
BMC Developmental Biology 2013, 13:6 doi:10.1186/1471-213X-13-6Published: 9 February 2013
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.