Anna Jazwinska Müller
Office PER 05 - 0.346B
+41 26 300 8890
Injuries to human organs, such as the limbs and the heart, result in persistent pathologic conditions. By contrast, zebrafish can completely reconstitute parts of their fins, hearts, retinas and spinal cords. Regeneration in zebrafish predominantly relies on the intrinsic plasticity of mature tissues. This property involves activation of the remaining tissue at the site of injury to promote cell division, cell migration and replacement of the missing structures. Which biological mechanisms guide the mature cells through the regeneration process? How do systemic factors modulate this process? Do regenerative programs of different organs rely on conserved mechanisms? In our research, we address these questions focusing on heart and fin regeneration in zebrafish. Our methods rely on pharmacological approaches and transgenic animals.
Adult zebrafish can regenerate their hearts within 1 to 2 months after damage. Several years ago, our laboratory established a cryoinjury-induced myocardial infarction model in zebrafish, whereby a freezing-thawing procedure destroys approx. 20% of the ventricle. We have since identified several signaling pathways that are required for heart restoration. We also found specific extracellular matrix components that are beneficial for regeneration. Our experiments revealed that the myocardium adjacent to the injury undergoes dedifferentiation, during which embryonic cardiac programs become reactivated to give rise to new tissue. We also reported that the natural power of heart regeneration in zebrafish can be suppressed by a daily hour of stress, such as crowding. By contrast, preconditioning, the application of a small remote noxious stimulus before injury, boosts heart regeneration. We are currently investigating the regenerative capacity of specific cardiac cell populations and comparing the restorative programs of different fish species.
The zebrafish fin is a multi-tissue appendage, the correct pattern and size of which can be restablished within 3 weeks after amputation. First, the fin margin is covered by a wound epithelium, and next a proliferative blastema arises by dedifferentiation of stump tissues near the amputation. Our laboratory identified signalling pathways that orchestrate proliferation, migration and patterning of different tissues in the regenerating fin. Furthermore, we identified that chromatin modification is critical for redifferentiation of blastema cells. Regarding extracellular matrix, we characterized the dynamics and regulation of the regeneration of actinotrichia, which are fin-specific skeletal structures. Our fate mapping experiments demonstrated that the activated mesenchyme of the stump gives rise to the blastema. We are currently investigating which adhesion mechanisms organize the different cells types during fin regeneration.