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Elife. 2017 Jul 25;6. pii: e25681. doi: 10.7554/eLife.25681.

Elastic force restricts growth of the murine utricle.

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Howard Hughes Medical Institute and Laboratory of Sensory Neuroscience, The Rockefeller University, New York, United States.
Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine of the University of Southern California, Los Angeles, United States.


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.


Hippo signaling; Yap; computational biology; developmental biology; growth control; hair cell; inner ear; mouse; stem cells; systems biology; utricle

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