Descrizione del progetto
Prossimità e capacità di rigenerazione dei tessuti
È importante notare che le parti amputate che sono distanti dal busto tendono a rigenerarsi a una velocità inferiore rispetto a quelle più vicine a esso. Come principale motivazione alla base di questa osservazione, è stata proposto un gradiente differenziale delle molecole della superficie cellulare, e quindi delle adesioni intercellulari. Il progetto ProxDistReg, finanziato dall’UE, si propone di studiare le proprietà biomeccaniche dei tessuti e il modo in cui influiscono sulla rigenerazione. I ricercatori impiegheranno la specie delle salamandre degli assolotti messicani come organismo modello e condurranno un’analisi dettagliata sugli arti amputati a livello di biologia, fisiologia ed espressione genica delle cellule. Il lavoro fornirà informazioni importanti sulla rigenerazione dei tessuti e coadiuverà la progettazione futura di biomateriali.
Obiettivo
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.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
01069 Dresden
Germania