Descripción del proyecto
Proximidad y capacidad de regeneración tisular
Curiosamente, las estructuras amputadas que se encuentran más alejadas del torso suelen regenerarse a un ritmo más lento que aquellas situadas más cerca. Como principal motivo de esta observación se ha planteado un gradiente diferencial de las moléculas de la superficie celular y, por tanto, adhesiones intercelulares. El objetivo del proyecto ProxDistReg, financiado con fondos europeos, es investigar las propiedades biomecánicas de los tejidos y cómo afectan a la regeneración. Los investigadores utilizarán la especie de salamandra «Axolotl mexicanum» como organismo modelo y realizarán un extenso análisis de extremidades amputadas desde el punto de vista de la biología celular, la fisiología y la expresión génica. Este trabajo permitirá obtener importante información sobre la regeneración tisular y contribuirá al diseño de nuevos biomateriales.
Objetivo
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.
Ámbito científico
Programa(s)
Régimen de financiación
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
01069 Dresden
Alemania