The Mechanical Control Of Tissue Regeneration and Polarity Re-establishment


Supervising PI

Yanlan Mao (website)

ESR10 Filippos Ioannou

Project Description

How mechanical forces influence wound healing after injury is still relatively unexplored, especially in 3-dimensions (3D). In this project we aim to dissect the relative mechanical contributions of the apical purse string and basolateral contractile structures to wound closure.

We will utilize novel techniques in Drosophila wing disc culture to live-image the regeneration process. We can monitor the cell division, cell shape and cytoskeletal changes by imaging actin (LifeAct-GFP), myosin (Sqh-GFP), adhesion molecules (e.g. E-cadherin-GFP), and changes in polarity complexes (e.g. Lgl-GFP, Scrib-GFP, Baz-mCherry). We will use state-of-the-art laser ablation and microscopy techniques to measure the changes in tension properties of the tissue. We have recently developed a unique tissue stretcher that can be used to culture the disc ex vivo whilst under compression or stretch. This will allow us to answer whether applying an external controlled force can alter the regeneration process and localization of polarity complexes. The aim is to complement experiments by developing a computational model of tissue regeneration. We will use an existing vertex model that our lab has developed, and also collaborate with Nate Goehring to develop new models of mechanical control of polarity establishment. Data from the experimental measurements will be used to parameterize the model, and predictions generated by the model can be tested in vivo – a constant 2-way interplay.

Objectives

Investigating the role of mechanical forces in tissue regeneration and polarity re-establishment.

Summary of Results

In order to dissect the relative mechanical contributions of the apical purse string and basolateral contractile structures to wound closure, the ESR, Filippos Ioannou, developed a new computational 3D cellular scale mechanical model of epithelia. In this model, cell centres form a mechanical network, as well as the vertices. This hybrid model allows us to tune the mechanical properties of the cell bulk as well as the cortical network. Using this model, the ESR simulated wound closure and parameterised it to represent the wing disc. He systematically changed apical forces vs basolateral forces to show how it affects wound closure rates and cell shape changes around the wound. Interestingly, he found that basolateral forces have a critical role in driving the dynamic cell shape changes during wound closure and to drive the most efficient wound closure

References

  1. Tetley RJ, Staddon MF, Banerjee S, Mao Y: Tissue Fluidity Promotes Epithelial Wound Healing. 2018. bioRxiv 433557.
  2. Mao Y, Tournier AL, Hoppe A, Kester L, Thompson BJ, Tapon N. Differential proliferation rates generate patterns of mechanical tension that orient tissue growth. EMBO J. 2013 Oct 30;32(21):2790–803.
  3. Mao Y, Tournier AL, Bates PA, Gale JE, Tapon N, Thompson BJ. Planar polarization of the atypical myosin Dachs orients cell divisions in Drosophila. Genes Dev. 2011 Jan 15;25(2):131–6.