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Molecular and cellular bases of heart regeneration in the zebrafish


Regeneration is a complex biological process by which animals restore the shape, structure, and function of body parts lost to injury or experimentally amputated. Only a few vertebrate species retain a significant regenerative capacity during adulthood. With respect to the heart, the extraordinary ability of newts to regenerate significant sections of the heart has been known for over 30 years.

However, the molecular and cellular mechanisms underlying this phenomenon remain largely unexplored, most probably owing to the intrinsic experimental difficulties and relative lack of genetic tools in this model system. Recently, it has been shown that adult zebrafish also display a remarkable ability to regenerate extensive portions of the heart after amputation.

In this project, we propose to take advantage of the powerful tools of genetic manipulation, genomic analysis, in vivo imaging, and reverse-genetics mutagenesis screenings available in the zebrafish, to undertake the following specific aims:
1) to identify and characterize the molecular mechanisms associated with the regenerative response of the zebrafish heart;
2) to characterize the changes in cell behavior dynamics associated with zebrafish heart regeneration;
3) to identify novel genes required for regeneration in the zebrafish.

We feel confident that detailed analyses of zebrafish heart regeneration, such as the one proposed herein, in addition to bolstering our understanding of this fascinating biological phenomenon, will provide valuable clues for the implementation of strategies of regenerative medicine.

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