Project description DEENESFRITPL Proximity and tissue regeneration capacity Intriguingly, amputated structures that are far from the torso tend to regenerate at a slower pace compared to structures that are closer to the torso. A differential gradient of cell surface molecules, and hence intercellular adhesions, has been proposed as the main reason behind this observation. The EU-funded ProxDistReg project aims to investigate the biomechanical properties of tissues and how they affect regeneration. Researchers will employ the salamander species Axolotl mexicanum as a model organism and undertake an extensive analysis of amputated limbs at the cell biology, physiology, and gene expression levels. The work will provide important information on tissue regeneration and assist in the future design of biomaterials. Show the project objective Hide the project objective Objective In several regenerating organisms it has been observed that distally amputated structures grow slower than proximally amputated ones, resulting in an overall time of regeneration that is independent of the tissue to be reformed. This observation suggests that cell proliferation or cell size could be adjusted with the plane of amputation along the proximo-distal (PD) axis, leading to an interesting scaling behaviour. It has been proposed that positional identity in the limb may be encoded as a proximal-to-distal gradient of cell surface molecules, that would in turn alter intercellular adhesions. Thus, it is possible that such differential adhesions are associated to the control of cell growth during regeneration. The central aim of this proposal is to address this question by combining cell biology, mathematical and physical tools, with the ultimate goal of understanding how the biomechanical properties of tissues affect regeneration, which may have important implications for the design of biomaterials aimed at being used for regenerative medicine.We will tackle this question in the highly regenerative salamander species Axolotl mexicanum, in which limb regeneration is initiated regardless of the amputation plane, and the regenerating limb grows until its size matches the contralateral undamaged one. We will evaluate growth rate and cell cycle of regenerating limbs amputated at different levels, and mathematically describe cell proliferation patterns. We will characterize several cell surface and extracellular matrix molecules along the PD axis, and measure tissue mechanics in vivo. Furthermore, we will for the first time, evaluate the Hippo pathway in salamanders, an important modulator of cell growth in response to several physical inputs, as the causal link between increased tissue stiffness and decreased proliferation. Fields of science natural sciencesbiological sciencescell biologyengineering and technologyindustrial biotechnologybiomaterials Keywords Limb regeneration Proximo-distal axis Stiffness measurements Mechanotransduction Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2020 - Individual Fellowships Call for proposal H2020-MSCA-IF-2020 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator TECHNISCHE UNIVERSITAET DRESDEN Net EU contribution € 174 806,40 Address HELMHOLTZSTRASSE 10 01069 Dresden Germany See on map Region Sachsen Dresden Dresden, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 174 806,40
