Description du projet
Proximité et capacité de régénération tissulaire
Étonnamment, les structures amputées éloignées du torse tendent à se régénérer à un rythme plus lent par rapport aux structures situées plus près du torse. La principale raison proposée à l’origine de cette observation est l’existence d’un gradient différentiel de molécules de surface cellulaire et, par conséquent, d’adhésions intercellulaires. Le projet ProxDistReg, financé par l’UE, entend étudier les propriétés biomécaniques des tissus et la manière dont elles affectent à la régénération. Les chercheurs emploieront Axolotl mexicanum, une espèce de salamandre, comme organisme modèle et entreprendront une analyse approfondie des membres amputés à l’échelle de la biologie cellulaire, de la physiologie et de l’expression génétique. Les travaux fourniront des informations importantes sur la régénération tissulaire et contribueront à la conception future de biomatériaux.
Objectif
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.
Champ scientifique
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
01069 Dresden
Allemagne