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Mechanical feedback via pressure regulates organ size

Presented by: 
Sean Gregory Megason Harvard University
Thursday 17th September 2015 - 09:00 to 10:00
INI Seminar Room 1
Co-authors: Kishore Mosaliganti (), Ian Swinburne (), Tom Hiscock (), L. Mahadevan (Department of Physics and School of Engineering and Applied Science, Harvard University)

Animals develop tissues of precise size, shape, and symmetry despite noise in the underlying molecular and cellular processes. How tissue and organ-level feedback regulates this noise is largely unknown. The Megason lab combines quantitative imaging, physical theory and perturbations in zebrafish to study size control of the developing inner ear and neural tube.

In the inner ear, we find that transepithelial fluid flow creates hydrostatic pressure in the lumen leading to stress in the otic epithelium and expansion of the otic vesicle. Pressure, in turn, inhibits endolymph transport into the lumen. This negative feedback loop between pressure and fluid flux allows the otic vesicle to change growth rate in order to regulate natural or experimentally induced size variation. Furthermore, the shape of the inner ear is modulated by spatial-temporal patterning of actomyosin contractility allowing a common lumenal pressure to drive varying local epithelial strain rates. This work uncovers how molecular driven mechanisms such as osmotic force generation and actomyosin tension can regulate tissue level morphogenesis via hydraulic feedback to ensure robust control of organ size.

We also find evidence for pressure-based feedback in the neural tube but at a very different spatial scale. Here, pressure forces created by single cells in mitosis influence the fate of adjacent cells in order to properly balance proliferation and differentiation rates to generate the right number of neurons despite variation in the process.
University of Cambridge Research Councils UK
    Clay Mathematics Institute London Mathematical Society NM Rothschild and Sons