title: Thyroid hormone increases fibroblast growth factor receptor expression and disrupts cell mechanics in the developing organ of corti.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Section on Developmental Neuroscience, Laboratory of Cochlear Development, National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, MD, USA. Katherine.Szarama@stjude.org
authors: Katherine B
authors: KB
authors: Szarama
authors: Núria
authors: N
authors: Gavara
authors: Ronald S
authors: RS
authors: Petralia
authors: Richard S
authors: RS
authors: Chadwick
authors: Matthew W
authors: MW
authors: Kelley
mesh_terms: D051339:Actin Depolymerizing Factors / Q000502:physiology; D000199:Actins / Q000502:physiology; D000818:Animals; D005455:Fluorescent Antibody Technique; D007037:Hypothyroidism / Q000503:physiopathology; D051379:Mice; D018625:Microscopy, Atomic Force; D008870:Microtubules; D009925:Organ of Corti / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D010766:Phosphorylation; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D013963:Thyroid Hormones / Q000502:physiology*
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D017468:Receptors, Fibroblast Growth Factor; D013963:Thyroid Hormones
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