Elastic force restricts growth of the murine utricle

• Published in: eLife Vol. 6
• Main Authors: Gnedeva, Ksenia, Jacobo, Adrian, Salvi, Joshua D, Petelski, Aleksandra A, Hudspeth, A J
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 25-07-2017; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Animals; Apoptosis; Balance; Bands; Cell cycle; Cell Cycle Proteins; Cell division; Cell growth; Cell proliferation; Computational and Systems Biology; Developmental Biology and Stem Cells; Ears & hearing; Elasticity; Epithelium - embryology; Epithelium - growth & development; Equilibrium; Genetic aspects; growth control; hair cell; Health aspects; Hippo signaling; Inner ear; Kinases; Mice; Models, Theoretical; Morphogenesis; Nuclear transport; Phosphoproteins - metabolism; Saccule and Utricle - embryology; Saccule and Utricle - growth & development; Sensory epithelium; Signaling peptides and proteins; Transcription; Utricle; Vestibular system; Yap; YAP-Signaling Proteins; Yes-associated protein; computational biology; systems biology; mouse; stem cells; Hippo signaling; utricle; developmental biology; hair cell; growth control; Yap; inner ear
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.25681

Dysfunctions of hearing and balance are often irreversible in mammals owing to the inability of cells in the inner ear to proliferate and replace lost sensory receptors. To determine the molecular basis of this deficiency we have investigated the dynamics of growth and cellular proliferation in a murine vestibular organ, the utricle. Based on this analysis, we have created a theoretical model that captures the key features of the organ's morphogenesis. Our experimental data and model demonstrate that an elastic force opposes growth of the utricular sensory epithelium during development, confines cellular proliferation to the organ's periphery, and eventually arrests its growth. We find that an increase in cellular density and the subsequent degradation of the transcriptional cofactor Yap underlie this process. A reduction in mechanical constraints results in accumulation and nuclear translocation of Yap, which triggers proliferation and restores the utricle's growth; interfering with Yap's activity reverses this effect.