Title | Elastic force restricts growth of the murine utricle. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Gnedeva K, Jacobo A, Salvi JD, Petelski AA, Hudspeth AJ |
Journal | Elife |
Volume | 6 |
Date Published | 2017 07 25 |
ISSN | 2050-084X |
Keywords | Adaptor Proteins, Signal Transducing, Animals, Elasticity, Epithelium, Mice, Models, Theoretical, Morphogenesis, Phosphoproteins, Saccule and Utricle |
Abstract | 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. |
DOI | 10.7554/eLife.25681 |
Alternate Journal | Elife |
PubMed ID | 28742024 |
PubMed Central ID | PMC5550282 |
Grant List | T32 DC009975 / DC / NIDCD NIH HHS / United States / HHMI / Howard Hughes Medical Institute / United States F30 DC013468 / DC / NIDCD NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States |
Submitted by kej2006 on June 6, 2018 - 4:10pm