Project description
Role of the extracellular matrix as a guide of regeneration in axolotl
Funded by the Marie Skłodowska-Curie Actions programme, the AxoMatrx project will use the axolotl model for regeneration to assess the initiation of regenerative responses, deciphering which components are important for the formation of the blastemal stem-cell niche. Specifically, researchers will address the role of the extracellular matrix (ECM) in the regulation of the limb regenerative response. They will characterise active ECM components across distinct stages of limb regeneration to create an ECM atlas of extracellular changes associated with the healing process. The data set proteins that are important for the regenerative response will be identified in depletion experiments using axolotl regeneration and by the ability to induce regeneration in the ectopic limb growth model.
Objective
How do dynamic changes of the extracellular matrix guide regenerative events in Axolotl?
To what extent the dedifferentiation of mature cells is an intrinsic property of the cells or a product of interaction with the microenvironment is an exigent question in the regeneration field.
In this project I will assess what initiates the regenerative response with an emphasis on deciphering what components are important for formation of the blastemal stem cell niche. Specifically, I will address whether ECM actively regulates the limb regenerative response or is merely a bystander. Although the importance of MMPs and ECM components in limb regeneration has been reported several times, few attempted to understand the role of ECM as signaling hub rather than as a “passive wall”.
To address this, I will use tools developed in the Tanaka lab and combine those with my ECM expertise. I will characterize active ECM components during several distinct stages of limb regeneration to create an ECM “atlas” depicting extracellular changes during healing. I will use the obtained dataset to identify proteins which are important for the regenerative response by depleting these factors during axolotl regeneration and by testing their ability to induce ectopic limb growth using the Accessory Limb Model. Lastly, I will attempt to translate the axolotl findings to the mammalian setting and facilitate regeneration in a non-regenerating context.
Surprisingly to date, no systemic characterization of extracellular molecules has been reported in regenerative systems, nor was any axolotl regenerative cue yet successfully translated to mammals. Thus, this characterization and candidate identification have far-reaching implications for both development and regenerative biology.
Fields of science
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
1030 Wien
Austria